AU2010249298A1 - Methods of treating platinum-resistant recurrent ovarian cancer with 4-iodo-3-nitrobenzamide in combination with an anti-metabolite and a platinum compound - Google Patents

Abstract

The present invention provides a method of treating platinum-resistant ovarian cancer, including recurrent ovarian cancer, in a patient, comprising administering to the patient having ovarian cancer an effective amount of 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof; gemcitabine; and carboplatin.

Description

1 Regulation 3.2 AUSTRALIA PATENTS ACT, 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT ORIGINAL Name of Applicant: BIPAR SCIENCES, INC. Actual Inventor: Charles BRADLIY Address for service in AJ PA RK, Level 11, 60 Marcus Clarke Street, Canberra ACT Australia: 2601, Australia Invention 'Title: ME'PTIODS 01F RIEl EATING PIAINUM-RESISTANT RFCURUE'i NTOVARIAN CANCER WITH 4-01D0-3 N ITROBEN ZAMIDE iN C0 MBINAT I ON WiI H AN ANII-METABOLIT AND A. PLIATINUM COMPOUND The following statement is a full description of this invenion, including he best method of performing it known to us. 21236/2955256 iDOC METHODS OF TREATING PLATINUM-RESISTANT RECURRENT OVARIAN CANCER WITH 4-IODO-3-NITROBENZAMIDE IN COMBINATION WITH AN ANTI-METABOLITE AND A PLATINUM COMPOUND RELATED APPLICATION [0001] This application claims priority to U.S. Provisional Application No. 61/351,772, filed June 4, 2010, the contents of which are hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION 10002] Cancer is a complex family of diseases affecting nearly every tissue in the body and characterized by aberrant control of cell growth. The annual incidence of all cancer types is estimated to be in excess of 1.3 million cases in the United States alone. While a number of first line therapies for the treatment of different types of cancer have been deployed with varying degrees of success, including surgical resection, radiation therapy, chemotherapy, and hormone therapy, it remains the second leading cause of death in the U.S., with an estimated 560,000 Americans dying from cancer every year. 10003] Malignant uterine neoplasms containing both carcinomatous and sarcomatous elements are designated in the World Health Organization (WHO) classification of uterine neoplasms as carcinosarcomas. An alternative designation is malignant mixed Mullerian tumor (MMMT). Carcinosarcomas also arise in the ovaries, Fallopian tubes, cervix, peritoneum, as well as in other non-gynecologic sites, but with a much lower frequency than in the uterus. These tumors are highly aggressive and have a poor prognosis. Most uterine carcinosarcomas are monoclonal, with the carcinomatous element being the key element and the sarcomatous component derived from the carcinoma or from a stein cell that undergoes divergent differentiation (i.e., metaplastic carcinomas). The sarcomatous component is either homologous (composed of tissues normally found in the uterus) or heterologous (containing tissues not normally found in the uterus, most commonly malignant cartilage or skeletal muscle). 100041 Previous studies investigating a number of single agents in carcinosarcoma of the uterus have reported the following response rates: etoposide (6.5%); doxorubicin (9.8%); cisplatin (18%); ifosfamide (32.2%); paclitaxel (18.2%); and topotecan (10%). Thus the three most active agents discovered to date include cisplatin, ifosfamide, and paclitaxel. A randomized phase III trial comparing ifosfamide to ifosfamide plus cisplatin showed an 2 increased response rate (36% vs. 54%), a slight improvement in median progression-free survival (PFS) (4 vs. 6 months, p=0.02), but no improvement in median survival (7.6 vs. 9.4 months, p=0.07). A second randomized trial evaluated the role of paclitaxel. In this study, patients are randomized to receive ifosfamide versus the combination of ifosfamide plus paclitaxel and showed an increased response rate (29% vs. 45%), improvement in median progression-free survival (3.6 vs. 5.8 months, p=0.03), and improvement in median survival (8.4 vs. 13.5 months, p=0.03). The use of ifosfamide is cumbersome and results in significant toxicity. 100051 In a related disease, endometrial carcinoma, there have been several randomized studies addressing the issue of optimal therapy. These studies have focused on three active agents identified in phase II trials: doxorubicin, platinum agents, and paclitaxel. In one study, 281 women are randomized to doxorubicin alone (60 mg/m 2 ) versus doxorubicin (60 mg/m2) plus cisplatin (50 mg/m 2 ) (AP). There is a statistically significant advantage to combination therapy with regard to response rate (RR) (25% versus 42%; p=0.00 4 ) and PFS (3.8 vs 5.7 months; FIR 0.74 [95% CI 0.58, 0.94; p= 0

.

14 ), although no difference in OS is observed (9 vs 9.2 months). Paclitaxel had significant single agent activity with a response rate of 36% in advanced or recurrent endometrial cancer. Thus 317 patients are randomized to paclitaxel and doxorubicin or the standard arm. This trial failed to demonstrate a significant difference in RR, PFS, or OS between the two arms, and AP remained the standard of care. However, since both platinum and paclitaxel had demonstrated high single agent activity, there is as strong interest in including paclitaxel and cisplatin in a front-line regimen for advanced and recurrent endometrial cancer, Subsequently, another study randomized 263 patients to AP versus TAP: doxorubicin (45 mg/m 2 ) and cisplatin (50 mg/n 2 ) on day 1, followed by paclitaxel (160 mg/n 2 IV over 3 hours) on day 2 (with G-CSF support). TAP is superior to AP in terms of ORR (57% vs 34%; p<0.01), median PFS (8.3 vs 5.3 months; p<0.01) and OS with a median of 15.3 (TAP) versus 12.3 months (AlP) (p=0.0 3 7 ). This improved efficacy came at the cost of increased toxicity. [0006] Although there are limited therapeutic options for cancer treatment generally, recurrent, advanced or persistent uterine and ovarian cancers are especially difficult to treat because they can be refractory to standard chemotherapeutic treatments. Therefore, there is a need for effective cancer treatments generally, and for treatment of recurrent, advanced, or persistent cancers, such as ovarian or uterine cancers, in particular. 3 BRIEF SUMMARY OF THE INVENTION [00071 In one aspect, the present invention provides a method of treating platinum-resistant recurrent ovarian cancer in a patient, comprising administering to the patient having ovarian cancer an effective amount of: (i) 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof; (ii) gemcitabine; and (iii) carboplatin. In some embodiments, the effective amount is administered over a 21-day treatment cycle, wherein (i) the effective amount of carboplatin is administered to the patient at 4 mg/mlominutc (AUC 4) on day 1 of the treatment cycle; (ii) the effective amount of gemcitabine is administered to the patient at a dose of 1000 mg/m2 on days 1 and 8 of the treatment cycle; and (iii) the effective amount of 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof is administered to the patient at a dose of 5.6 mg/kg twice weekly on days 1, 4, 8, and 11 of the treatment cycle. In some embodiments, the effective amount produces at least one therapeutic effect selected from the group consisting of reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, stable disease, increase in overall response rate, or a pathologic complete response. In some embodiments, a comparable clinical benefit rate (CBR = CR (complete remission) + PR (partial remission) + SD (stable disease) > 6 months) is obtained compared to treatment with gemcitabine and carboplatin administered without 4-iodo-3-nitrobenzamide. In some embodiments, the improvement of clinical benefit rate is about 20% or higher. In some embodiments, the therapeutic effect is an increase in overall response rate. In some embodiments, the overall response rate is greater than 15%. In some embodiments, the overall response rate is greater than 20%. In some embodiments, the overall response rate is greater than 30%. In some embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, immunotherapy, nanotherapy or a combination thereof. In some embodiments, the method further comprises administering to the patient gamma irradiation. In some embodiments, the platinum-resistant recurrent ovarian cancer is selected from the group consisting of epithelial, germ cell, and stromal cell tumors. In some embodiments, the the platinum-resistant recurrent ovarian cancer is metastatic. 100081 In some embodiments, the platinum-resistant recurrent ovarian cancer is deficient in homologous recombination DNA repair. In some embodiments, the homologous recombination DNA repair-deficient platinum-resistant recurrent ovarian cancer is BRCA 4 deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is BRCAl-deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is BRCA2-deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is both BRCA1 -deficient and BRCA2-deficient. [0009] In one aspect, the present invention provides a method of treating platinum-resistant ovarian cancer in a patient, comprising administering to the patient having ovarian cancer an effective amount of: (i) 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof; (ii) gemcitabine; and (iii) carboplatin. In some embodiments, the effective amount is administered over a 21-day treatment cycle, wherein (i) the effective amount of carboplatin is administered to the patient at 4 mg/ml-minute (AUC 4) on day I of the treatment cycle; (ii) the effective amount of gemcitabine is administered to the patient at a dose of 1000 mg/m 2 on days I and 8 of the treatment cycle; and (iii) the effective amount of 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof is administered to the patient at a dose of 5.6 mg/kg twice weekly on days 1, 4, 8, and 11 of the treatment cycle. In some embodiments, the effective amount produces at least one therapeutic effect selected from the group consisting of reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, stable disease, increase in overall response rate, or a pathologic complete response. In some embodiments, a comparable clinical benefit rate (CBR = CR (complete remission) + PR (partial remission) + SD (stable disease) > 6 months) is obtained compared to treatment with gemcitabine and carboplatin administered without 4-iodo-3-nitrobenzamide. In some embodiments, the improvement of clinical benefit rate is about 20% or higher. In some embodiments, the therapeutic effect is an increase in overall response rate. In some embodiments, the overall response rate is greater than 20%. In some embodiments, the overall response rate is greater than 15%. In some embodiments, the overall response rate is greater than 30%. In some embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, immunotherapy, nanotherapy or a combination thereof. In some embodiments, the method further comprises administering to the patient gamma irradiation. In some embodiments, the platinum-resistant ovarian cancer is selected from the group consisting of epithelial, germ cell, and stromal cell tumors. In some embodiments, the platinum-resistant ovarian cancer is recurrent ovarian cancer. In some embodiments, the platinum-resistant ovarian cancer is metastatic. 5 [0010] In some embodiments, the platinum-resistant ovarian cancer is deficient in homologous recombination DNA repair. In some embodiments, the homologous recombination DNA repair-deficient platinum-resistant ovarian cancer is BRCA deficient. In some embodiments, the BRCA-deficient platinum-resistant ovarian cancer is BRCA 1 deficient. In some embodiments, the BRCA-deficient platinum-resistant ovarian cancer is BRCA2-deficient. In some embodiments, the BRCA-deficient platinum-resistant ovarian cancer is both BRCA1-deficient and BRCA2-deficient. 100111 In another aspect is provided the use of the pharmaceutical compositions described herein for the manufacture of a medicament for treating platinum-resistant ovarian cancer. For example, use as provided herein with respect to the methods described herein. [0012] In a further aspect is provided the use of 4-iodo-3-nitrobenzamide, a metabolite thereof, or a pharmaceutically acceptable salt or solvate thereof, in combination with any one of the antimetabolites and with any one of the platinum compounds described herein, a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment or prevention of platinum-resistant ovarian cancer as described herein. [0013] In some aspects are provided synergistic compositions used for treating platinum resistant ovarian cancer in a patient comprising a) 4-iodo-3-nitrobenzamide, or a metabolite thereof, or a pharmaceutically acceptable salt or solvate thereof, b) an antimetabolite, or pharmaceutically acceptable salt or solvate thereof, and (C) a platinum compound to said patient, wherein the alkylating agent is selected from the group consisting of citabine, capecitabine, gemeitabine or valopicitabine), and wherein the platinum compound is selected from the group consisting of cisplatin; cis-diamminediaquoplatinum (11)-ion; chloro(diethylenetriamine)-platinum (II) chloride; dichloro(ethylenediamine)-platinum (1I); diammine( 1,1 -cyclobutanedicarboxylato) platinum (11) (carboplatin); spiroplatin; iproplatin; diammine(2-ethylmalonato)platinum (11); ethylenediaminemal onatoplatinum (II); aqua(I,2 diami nodicyclohexane)suIlfatoplatinum (II); aqua(1,2 diaminodicyclohexane)malonatoplatinum (II); (1,2-di aminocyclohexane)malonatopl atinum (II); (4-carboxyphthalato) (1,2-diaminocyclohexane) platinum (II); (1,2-diaminocyclohexane) (isocitrato)platinum (II); (1,2-diaminocyclohexane)oxalatoplatinum (II); ormaplatin; tetraplatin; carboplatin, nedaplatin and oxaliplatin. 6 INCORPORATION BY REFERENCE [00141 All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application is specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE FIGURES [0015] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [0016] FIGURE 1 shows tumor response after 4 cycles of 4-iodo-3-nitrobenzamide (BA) treatment in combination with topotecan in a patient with ovarian cancer. 10017] FIGURE 2 shows PA RP inhibition in peripheral mononuclear blood cells (PMBCs) from patients receiving 4-iodo-3-nitrobenzamide. DETAILED DESCRIPTION 100181 As used herein, the term "platinum-resistant" refers to a type of ovarian cancer (e.g., recurrent ovarian cancer). The current standard of care for first-line chemotherapy of ovarian cancer is a combination of a platinum compound (e.g., cisplatin, carboplatin, and oxaliplatin) with a taxane. The majority of newly-diagnosed ovarian cancer patients will respond to first line platinum-based and paclitaxel chemotherapy. However, 50-80% of the patients who respond to this combination therapy will eventually relapse. See, e.g., Herzog, "Update on the role of topotecan in the treatment of recurrent ovarian cancer," The Oncologist 7(Suppl. 5):3-10 (2002). Patients who relapse within six months are less likely to respond to a second round of platinum-based therapy. Therefore, advanced ovarian cancer tumors that have recurred are classified as being "platinum-sensitive" if relapse occurs more than six months after the last dose of platinum-based therapy, "platinum-resistant" if relapse occurs less than or equal to six months after the last dose of platinum-based therapy, and "platinum refractory" if no response or disease regression occurs during initial platinum-based therapy. [0019] As used herein "surgery" refers to any therapeutic or diagnostic procedure that involves methodical action of the hand or of the hand with an instrument, on the body of a human or other mammal, to produce a curative, remedial, or diagnostic effect. 7 [0020] "Radiation therapy" refers to exposing a patient to high-energy radiation, including without limitation x-rays, gamma rays, and neutrons. This type of therapy includes without limitation external-beam therapy, internal radiation therapy, implant radiation, brachytherapy, systemic radiation therapy, and radiotherapy. [0021] "Chemotherapy" refers to the administration of one or more anti-cancer drugs such as, antineoplastic chemotherapeutic agents, chemopreventative agents, and/or other agents to a patient with platinum-resistant ovarian cancer (e.g, recurrent ovarian cancer) by various methods, including intravenous, oral, intramuscular, intraperitoneal, intravesical, subcutaneous, transdermal, buccal, or inhalation or in the form of a suppository. Unless clearly dictated otherwise by context, "chemotherapy" as used herein is not intended to refer to the administration of 4-iodo-3-nitrobenzamide, an antimetabolite (e.g., gemcitabine), and a platinum compound (e.g., carboplatin) as described herein. Chemotherapy may be given prior to surgery to shrink a large tumor prior to a surgical procedure to remove it, prior to radiation therapy, or after surgery and/or radiation therapy to prevent the growth of any remaining ovarian cancer cells in the body. Chemotherapy may also occur during the course of radiation therapy. 10022] The terms "effective amount" or "pharmaceutically effective amount" refer to a sufficient amount of an agent to provide the desired biological, therapeutic, and/or prophylactic result. That result can be reduction and/or alleviation of one or more of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an "effective amount" for therapeutic uses is the amount of a) 4-iodo-3 nitrobenzamide or a metabolite thereof or a pharmaceutically acceptable salt or solvate thereof; b) an antimetabolite (e.g., gemcitabine), or pharmaceutically acceptable salt or solvate thereof; and c) a platinum compound (e.g., carboplatin) provided herein, or a composition comprising a) 4-iodo-3-nitrobenzamide or a metabolite thereof or a pharmaceutically acceptable salt or solvate thereof; b) an antimetabolite (e.g., gemcitabine), or pharmaceutically acceptable salt or solvate thereof; and c) a platinum compound (e.g., carboplatin) provided herein required to provide a clinically significant decrease in the platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) or slowing of progression of the platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer). [0023] "Metabolite" refers to a compound produced through any in vitro or in vivo metabolic process which results in a product that is different in structure than that of the starting compound. In other words, the term "metabolite" includes the metabolite compounds of 4-iodo-3-nitrobenzamide. A metabolite can include a varying number or types of 8 substituents that are present at any position relative to a precursor compound. In addition, the terms "metabolite" and "metabolite compound" are used interchangeably herein. 100241 By "pharmaceutically acceptable" is meant a material which is not biologically or otherwise undesirable, i.e., the material may be administered to a patient without causing any undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. [00251 The term "treating" and its grammatical equivalents as used herein include achieving a therapeutic benefit and/or a prophylactic benefit. By therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated. For example, in a patient having platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer), therapeutic benefit includes eradication or amelioration of the underlying ovarian cancer, e.g., slowing of progression of the ovarian cancer. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder (e.g., ovarian cancer) such that an improvement is observed in the patient, notwithstanding the fact that the patient may still be afflicted with the underlying disorder (e.g., ovarian cancer). For prophylactic benefit, a method of the invention may be performed on, or a composition of the invention administered to a patient at risk of developing platinum resistant ovarian cancer (e.g., recurrent ovarian cancer), or to a patient reporting one or more of the physiological symptoms of platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer), even though a diagnosis of platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) may not have been made. In some embodiments, the patient being treated has been diagnosed with a platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) described herein. [0026] Reference to "about" a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to "about X" includes description of "X". [00271 As used herein and in the appended claims, the singular forms "a," "or," and "the" include plural referents unless the context clearly dictates otherwise. It is understood that aspects and variations of the invention described herein include "consisting" and/or "consisting essentially of' aspects and variations. Treatment of Ovarian Cancer 9 [0028] Ovarian cancer is the leading cause of death from gynecologic malignancy. It is the eighth most common cancer in women, with approximately 21,550 new diagnoses and 14,600 deaths in the United States in 2009. Ovarian cancer is difficult to detect in its early stages; only about 20 percent of ovarian cancers are found before tumor growth has spread into adjacent tissues. By the time ovarian cancer has progressed to later stages of the disease, the long-term prognosis is generally poor, with a five-year survival rate of-30%. Despite high initial response to the first line neoadjuvant chemotherapy-a combination of a platinum compound and a taxane-recurrence is common, with a median progression-free survival of about eighteen months. [0029] There are three basic types of ovarian tumors: epithelial, germ cell, and stromal cell tumors. Epithelial tumors start from the cells that cover the outer surface of the ovary; most ovarian tumors are epithelial cell tumors. Germ cell tumors start from the cells that produce the eggs. Stromal tumors start from cells that hold the ovary together and make the female hormones. [00301 A significant risk factor for ovarian cancer includes deficiencies in DNA repair via homologous recombination, such as mutations in the BRCA1 or BRCA2 gene. Those genes were originally identified in families with multiple cases of breast cancer, but have been associated with approximately 5 to 10 percent of ovarian cancers. [0031] Possible treatments for ovarian cancer include surgery, immunotherapy, chemotherapy, hormone therapy, radiation therapy, or a combination thereof. Surgical procedures for the treatment of ovarian cancer include debulking, and a unilateral or bilateral oophorectomy and/or a unilateral or bilateral salpigectomy. Anti-cancer drugs that have also been used to treat ovarian cancer include cyclophosphamide, etoposide, altretamine, and ifosfamide. Hormone therapy with the drug tamoxifen is also used to shrink ovarian tumors. Radiation therapy optionally includes external beam radiation therapy and/or brachytherapy. 10032] In one aspect, provided herein are methods of treating platinum-resistant recurrent ovarian cancer in a patient, comprising administering to the patient a PARP inhibitor, an antimetabolite, and a platinum compound. In some embodiments, the PARP inhibitor is a PARP- 1 inhibitor. In some embodiments, the PARP- I inhibitor is 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof, In some embodiments, the antinietabolite is selected from the group consisting of citabine, capecitabine, gemcitabine or valopicitabine. In some embodiments, the antimetabolite is gemeitabine. In some embodiments, the platinum compound is selected from the group consisting of cisplatin; cis diamminediaquoplatinum (II)-ion; chloro(diethylenetriamine)-platinum (II) chloride; 10 dichloro(ethylenediamine)-platinum (II); diammine(1, 1 -cyclobutanedicarboxylato) platinum (II) (carboplatin); spiroplatin; iproplatin; diammine(2-ethylmalonato)platinum (II); ethylenediaminemalonatoplatinum (II); aqua(1,2-diaminodicyclohexane)sulfatoplatinum (II); aqua(1,2-diaminodicyclohexane)malonatoplatinum (II); (1,2 diaminocyclohexane)malonatoplatinum (II); (4-carboxyphthalato)(1,2-diaminocyclohexane) platinum (II); (1,2-diaminocyclohexane)-(isocitrato)platinum (II); (1,2 diaminocyclohexane)oxalatoplatinum (II); ormaplatin; tetraplatin; carboplatin, nedaplatin and oxaliplatin, and preferred is carboplatin or oxaliplatin. In some embodiments, the platinum compound is carboplatin. [0033] In some embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, immunotherapy, nanotherapy or a combination thereof. In some embodiments, the method further comprises administering to the patient gamma irradiation. In some embodiments, the platinum-resistant recurrent ovarian cancer is selected from the group consisting of epithelial, germ cell, and stromal cell tumors. In some embodiments, the the platinum-resistant recurrent ovarian cancer is metastatic. [0034] In some embodiments, the platinum-resistant recurrent ovarian cancer is deficient in homologous recombination DNA repair. In some embodiments, the homologous recombination DNA repair-deficient platinum-resistant recurrent ovarian cancer is BRCA deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is BRCAI-deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is BRCA2-deficient. In some embodiments, the BRCA-deficient platinum-resistant recurrent ovarian cancer is both BRCA 1 -deficient and BRCA2-deficient. [0035] In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, increase in overall response rate or stable disease. In some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor. In some embodiments, the improvement of clinical benefit rate is at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, or more. In some embodiments, the therapeutic effect is an increase in overall response rate. In some embodiments, the increase in overall response rate is 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or more. [0036] In some embodiments, the platinum-resistant ovarian cancer is a metastatic ovarian cancer. In some embodiments, a deficiency in a BRCA gene is detected in the ovarian cancer 11 patient. In some embodiments, the BRCA gene is BRCA 1. In other embodiments, the BRCA gene is BRCA-2. In yet other embodiments, the BRCA gene is BRCA-l and BRCA 2. In other embodiments, the deficiency is a genetic defect in the BRCA gene. In some embodiments, the genetic defect is a mutation, insertion, substitution, duplication or deletion of the BRCA gene. [0037] In some embodiments, the methods for treating platinum-resistant recurrent ovarian cancer further comprise administering a PARP inhibitor in combination with an anti-tumor agent. In some embodiments, the anti-tumor agent is an antitumor alkylating agent, antitumor antimetabolite, antitumor antibiotics, plant-derived antitumor agent, antitumor platinum complex, antitumor camptothecin derivative, antitumor tyrosine kinase inhibitor, monoclonal antibody, interferon, biological response modifier, hormonal anti-tumor agent, anti-tumor viral agent, angiogenesis inhibitor, differentiating agent, or other agent that exhibits anti-tumor activities, or a pharmaceutically acceptable salt thereof In some embodiments, the platinum complex is cisplatin, carboplatin, oxaplatin or oxaliplatin. In some embodiments, the antimetabolite is citabine, capecitabine, gemcitabine or valopicitabine. In some embodiments, the methods further comprise administering to the patient a PARP inhibitor in combination with more than one anti-tumor agent. In some embodiments, the anti-tumor agent is administered prior to, concomitant with or subsequent to administering the PARP inhibitor. In some embodiments, the anti-tumor agent is an anti angiogenic agent, such as Avastin or a receptor tyrosine kinase inhibitor including but not limited to Sutent, Nexavar, Recentin, ABT-869, and Axitinib. In some embodiments, the anti tumor agent is a topoisomerase inhibitor including but not limited to irinotecan, topotecan, or camptothecin. In some embodiments, the anti-tumor agent is a taxane including but not limited to paclitaxel, docetaxel and Abraxane. In some embodiments, the anti-tumor agent is an agent targeting Her-2, i, Herceptin or lapatinib. In some embodiments, the anti-tumor agent is a hormone analog, for example, progesterone. In some embodiments, the anti-tumor agent is tamoxifen, a steroidal aromatase inhibitor, a non-steroidal aromatase inhibitor, or Fulvestrant. In some embodiments, the anti-tumor agent is an agent targeting a growth factor receptor. in some embodiments, such agent is an inhibitor of epidermal growth factor receptor (EGFR) including but not limited to Cetuximab and Panitumimab. In some embodiments, the agent targeting a growth factor receptor is an inhibitor of insulin-like growth factor I (IGF-1) receptor (IGF1R) such as CP-751871. In other embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA 12 therapy, adjuvant therapy, neoadjuvant therapy, viral therapy, RNA therapy, immunotherapy, nanotherapy or a combination thereof. 10038] In some embodiments, the methods for treating platinum-resistant recurrent ovarian cancer further comprise administering a PARP inhibitor in combination with an anti-tumor agent. In some embodiments, the anti-tumor agent is an antitumor alkylating agent, antitumor antimetabolite, antitumor antibiotics, anti-tumor viral agent, plant-derived antitumor agent, antitumor platinum complex, antitumor camptothecin derivative, antitunor tyrosine kinase inhibitor, monoclonal antibody, interferon, biological response modifier, hormonal anti-tumor agent, angiogenesis inhibitor, differentiating agent, or other agent that exhibits anti-tumor activities, or a pharmaceutically acceptable salt thereof. In some embodiments, the platinum complex is cisplatin, carboplatin, oxaplatin or oxaliplatin. In some embodiments, the antimetabolite is citabine, capecitabine, gemcitabine or valopicitabine. In some embodiments, the methods further comprise administering to the patient a PARP inhibitor in combination with more than one anti-tumor agent. In some embodiments, the anti-tumor agent is administered prior to, concomitant with or subsequent to administering the PARP inhibitor. In other embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, viral therapy, RNA therapy, immunotherapy, nanotherapy or a combination thereof. [00391 In some embodiments, the treatment comprises a treatment cycle of at least 11 days, i.e. about 11 to about 30 days in length, wherein on from 1 to 10 separate days of the cycle, the patient receives about I to about 100 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, on from 1 to 10 separate days of the cycle, the patient receives about I to about 50 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, on from 1 to 10 separate days of the cycle, the patient receives about 1, 2, 3, 4, 6, 8 or 10, 12, 14, 16, 18 or 20 mg/kg of 4-iodo-3-nitrobenzamide. 10040] Some embodiments described herein provide a method of treating ovarian cancer in a patient having a deficiency in a BRCA gene, comprising during a 21 day treatment cycle on days 1, 4, 8 and 11 of the cycle, administering to the patient about 10 to about 100 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, the 4-iodo-3-nitrobenzamide is administered orally or as a parenteral injection or infusion, or inhalation. 13 100411 Some embodiments described herein provide a method of treating ovarian cancer in a patient having a deficiency in a BRCA gene, comprising: (a) establishing a treatment cycle of about 10 to about 30 days in length; (b) on from I to 10 separate days of the cycle, administering to the patient about 1 mg/kg to about 50 mg/kg of 4-iodo-3-nitrobenzamide, or a molar equivalent of a metabolite thereof. In some embodiments, the 4-iodo-3 nitrobenzamide is administered orally or as a parenteral injection or infusion, or inhalation. [0042j Some embodiments provided herein include a method of treating ovarian cancer in a patient in need of such treatment, comprising: (a) obtaining a sample from the patient; (b) testing the sample to determine if there is a deficiency in a BRCA gene; (c) if the testing indicates that the patient has a deficiency in a BRCA gene, treating the patient with at least one PARP inhibitor; and (d) if the testing does not indicate that the patient has a deficiency in a BRCA gene, selecting a different treatment option. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, increase in overall response rate, or stable disease. In some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor. In some embodiments, the clinical benefit rate is at least about 30%. In some embodiments, the PARP inhibitor is a PARP-l inhibitor. In other embodiments, the PARP-I inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4-iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the sample is a tissue or bodily fluid sample. In some embodiments, the sample is a tumor sample, a blood sample, a blood plasma sample, a peritoneal fluid sample, an exudate or an effusion. In some embodiments, the ovarian cancer is a metastatic ovarian cancer. In some embodiments, the BRCA gene is BRCA-1. In other embodiments, the BRCA gene is BRCA-2. In some embodiments, the BRCA gene is BRCA I and BRCA-2. In other embodiments, the deficiency is a genetic defect in the BRCA gene. In some embodiments, the genetic defect is a mutation, insertion, substitution, duplication or deletion of the BRCA gene. [0043] Some embodiments provide a method of treating ovarian cancer in a patient, comprising: (a) testing a sample from the patient for PARP expression; and (b) if the PARP expression exceeds a predetermined level, administering to the patient at least one PARP inhibitor. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In 14 some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor. In some embodiments, the improvement of clinical benefit rate is at least about 30%. In some embodiments, the PARP inhibitor is a PARP-1 inhibitor. In other embodiments, the PARP-1 inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4 iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the ovarian cancer is a metastatic ovarian cancer. Treatment of Uterine and Endometrial Cancer [0044] Malignant uterine neoplasms containing both carcinomatous and sarcomatous elements are designated in the World Health Organization (WHO) classification of uterine neoplasms as carcinosarcomas. An alternative designation is malignant mixed Mullerian tumor (MMMT). Most uterine carcinosarcomas are monoclonal, with the carcinomatous element being the key element and the sarcomatous component derived from the carcinoma or from a stem cell that undergoes divergent differentiation (i.e., metaplastic carcinomas). The sarcomatous component is either homologous (composed of tissues normally found in the uterus) or heterologous (containing tissues not normally found in the uterus, most commonly malignant cartilage or skeletal muscle). [0045] Previous studies investigating a number of single agents in carcinosarcoma of the uterus have reported the following response rates: etoposide (6.5%); doxorubicin (9.8%); cisplatin (18%); ifosfamide (32.2%); paclitaxel (18.2%); and topotecan (10%). Thus the three most active agents discovered to date include cisplatin, ifosfamide, and paclitaxel. A randomized phase III trial comparing ifosfamide to ifosfamide plus cisplatin showed an increased response rate (36% vs. 54%), a slight improvement in median progression-free survival (4 vs. 6 months, p=0.0 2 ), but no improvement in median survival (7.6 vs. 9.4 months, p=O.

0 7 ). A second randomized trial evaluated the role of paclitaxel. In this study, patients are randomized to receive ifosfamide versus the combination of ifosfamide plus paclitaxel and showed an increased response rate (29% vs. 45%), improvement in median progression-free survival (3.6 vs. 5.8 months, p=0.03), and improvement in median survival (8.4 vs. 13.5 months, p=0.03). The use of ifosfamide is cumbersome and results in significant toxicity. 100461 In a highly related disease, endometrial carcinoma, there have been several randomized studies addressing the issue of optimal therapy. These studies have focused on Is three active agents identified in phase U1 trials: doxorubicin, platinum agents, and paclitaxel. In one study, 281 women are randomized to doxorubicin alone (60 mg/m 2 ) versus doxorubicin (60 mg/in 2 ) plus cisplatin (50 mg/m 2 ) (AP). There is a statistically significant advantage to combination therapy with regard to response rate (RR) (25% versus 42%; p=0.004) and PFS (3.8 vs 5.7 months; HR 0.74 [95% CI 0.58, 0.94; p=0.1 4 ), although no difference in OS is observed (9 vs 9.2 months). Paclitaxel had significant single agent activity with a response rate of 36% in advanced or recurrent endometrial cancer. Thus 317 patients are randomized to paclitaxel and doxorubicin or the standard arm. This trial failed to demonstrate a significant difference in RR, PFS, or OS between the two arms, and AP remained the standard of care. However, since both platinum and paclitaxel had demonstrated high single agent activity, there is as strong interest in including paclitaxel and cisplatin in a front-line regimen for advanced and recurrent endometrial cancer, Subsequently, another study randomized 263 patients to AP versus TAP: doxorubicin (45 mg/m 2 ) and cisplatin (50 mg/n 2 ) on day 1, followed by paclitaxel (160 mg/m 2 IV over 3 hours) on day 2 (with G-CSF support). TAP is superior to AP in terms of ORR (57% vs 34%; p<0.01), median PFS (8.3 vs 5.3 months; p<0.0l) and OS with a median of 15.3 (TAP) versus 12.3 months (AP) (p=0.0 37 ). This improved efficacy, however, came at the cost of increased toxicity. Uterine Tumors 100471 Uterine tumors consist of the group of neoplasm that can be localized at the corpus, isthmus (the transition between the endocervix and uterine corpus) and cervix. The fallopian tubes and uterine ligaments may also undergo tumor transformation. Uterine tumors may affect the endometrium, muscles or other supporting tissue. Uterine tumors are histologically and biologically different and can be divided into several types. Uterine tumors may be histologically typed according to several classification systems. Those used most frequently are based on the WHO (World Health Organization) International Histological Classification of Tunours and on the ISGYP (International Society of Gynecological Pathologists). The most widely-accepted staging system is the FIGO (International Federation of Gynecology and Obstetrics) one. Classification 16 [00481 According to the World Health Organization ("WHO"), the main categories of uterine and cervical cancers are: epithelial tumors; mesenchymal tumors; mixed epithelial and mesenchymal tumors; and secondary tumors. The main uterine corpus categories, once again according to the WHO, are: epithelial tumors, mesenchyrnal tumors, mixed epithelial and mesenchymal tumors, trophoblastic tumors, and secondary tumors. Uterine cancer is the most common, specifically endometrial cancer of the uterine corpus. 10049] Uterine Corpus Neoplasia. The most common uterine corpus malignancy is the endometrial carcinoma (approximately 95%); sarcomas represent only 4% and heterologous tumors such as rhabdomyosarcomas, osteosarcomas and chondrosarcomas the remaining I%. [0050] Endometrial carcinoma has several subtypes that based on origin, differentiation, genetic background and clinical outcome. Endometrial carcinoma is defined as an epithelial tumor, usually with glandular differentiation, arising in the endometrium and which has the potential to invade the myometrium and spread to distant sites. Endometrial carcinoma can be classified as endometrioid adenocarcinoma, serous carcinoma, clear cell carcinoma, mucinous carcinoma, serous carcinoma, mixed types of carcinoma, and undifferentiated carcinoma. Endometrial carcinoma is an heterogeneous entity, comprising of: type I: endometrioid carcinoma : pre- and perimenopausal, estrogen dependent, associated to endometrial hyperplasia, low grade, indolent behaviour, representing about 80 % of the cases; type II: serous carcinoma : post-menopausal, estrogen independent, associated to atrophic endometrium, high grade, aggressive behaviour, representing about 10 % of the cases. Among other histologic types, type I includes mucinous and secretory carcinomas, whereas type II includes clear-cell carcinomas and adenosquamous carcinomas (Gurpide E, J Natl Cancer Inst 1991; 83: 405-416; Blaustein's Pathology of the Female Genital Tract, Kurman R.J. 4th ed. Springer-Verlag. New-York 1994). [0051] Uterine Cervix Neoplasia. Worldwide, invasive cervical cancer is the second most common female malignancy after breast cancer, with 500,000 new cases diagnosed each year. Uterine cervix cancers has several subtypes such as epithelial neoplasia and mesenchymal neoplasia. Etiology [0052] Carcinomas of the uterine cervix are thought to arise from precursor lesions, and different subtypes of human papilloma virus (HPV) are major etiological factors in disease pathogenesis. 17 [0053] Heterogeneity of uterine tumors provide a challenge to find and optimize the therapy to treat and cure these types of cancers and chemotherapeutic agent that are efficacious for other cancers are not efficacious for uterine tumors such as endometrial cancer. One of the examples could be Tamoxifen. Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely prescribed hormonal therapy treatment for breast cancer. Despite the benefits of tamoxifen therapy, almost all tamoxifen-responsive breast cancer patients develop resistance to therapy. In addition, tamoxifen displays estrogen-like effects in the endometrium increasing the incidence of endometrial cancer (Fisher B, Costantino JP, Redmond CK, et al., J Natl Cancer Inst 1994; 86:527-37; Shah YM, et al., Mol Cancer Ther. 2005 Aug;4(8):1239-49). [0054] In patients with persistent or recurrent nonsquamous cell carcinoma of the cervix, the study was undertaken by Gynecologic Oncology Group to estimate the antitumor activity of tamoxifen (L. R. Bigler, J. et al., (2004) International Journal of Gynecological Cancer 14 (5), 871-874). Tamoxifen citrate is administered at a dose of 10 mg per orally twice a day until disease progression or unacceptable side effects prevented further therapy. A total of 34 patients (median age: 49 years) are registered to this trial; two are declared ineligible. Thirty two patients are evaluable for adverse effects and 27 are evaluable for response. There are only six grades 3 and 4 adverse effects reported: leukopenia (in one patient), anemia (in two), emesis (in one), gastrointestinal distress (in one), and neuropathy (in one). The objective response rate is 11. 1 %, with one complete and two partial responses. In conclusion, tamoxifen appears to have minimal activity in nonsquamous cell carcinoma of the cervix. [0055] Accordingly, some embodiments described herein provide a method of treating uterine cancer or endometrial cancer in a patient, comprising administering to the patient at least one PARP inhibitor. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a uterine tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor. In some embodiments, the improvement of clinical benefit rate is at least about 30%. In some embodiments, the PARP inhibitor is a PARP-1 inhibitor. In other embodiments, the PARP-1 inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4 iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the uterine cancer is a metastatic uterine cancer. In some embodiments, the uterine cancer is recurrent, advanced or persistent. 1 8 10056] In some embodiments, the methods for treating uterine cancer or endometrial cancer further comprise administering a PARP inhibitor in combination with an anti-tumor agent. In some embodiments, the anti-tumor agent is an antitumor alkylating agent, antitumor antimetabolite, antitumor antibiotics, plant-derived antitumor agent, antitumor platinum complex, antitumor camptothecin derivative, antitumor tyrosine kinase inhibitor, monoclonal antibody, interferon, biological response modifier, hormonal anti-tumor agent, anti-tumor viral agent, angiogenesis inhibitor, differentiating agent, or other agent that exhibits anti tumor activities, or a pharmaceutically acceptable salt thereof. In some embodiments, the platinum complex is cisplatin, carboplatin, oxaplatin or oxaliplatin. In some embodiments, the antimetabolite is citabine, capecitabine, gemcitabine or valopicitabine, In some embodiments, the methods further comprise administering to the patient a PARP inhibitor in combination with more than one anti-tumor agent. In some embodiments, the anti-tumor agent is administered prior to, concomitant with or subsequent to administering the PARP inhibitor. In some embodiments, the anti-tumor agent is an anti-angiogenic agent, such as Avastin or a receptor tyrosine kinase inhibitor including but not limited to Sutent, Nexavar, Recentin, ABT-869, and Axitinib. In some embodiments, the anti-tumor agent is a topoisomerase inhibitor including but not limited to irinotecan, topotecan, or camptothecin. In some embodiments, the anti-tumor agent is a taxane including but not limited to paclitaxel, docetaxel and Abraxane. In some embodiments, the anti-tumor agent is an agent targeting Her-2, e.g., Herceptin or lapatinib. In some embodiments, the anti-tumor agent is a hormone analog, for example, progesterone. In some embodiments, the anti-tumor agent is tamoxifen, a steroidal aromatase inhibitor, a non-steroidal aromatase inhibitor, or Fulvestrant. In some embodiments, the anti-tumor agent is an agent targeting a growth factor receptor. In some embodiments, such agent is an inhibitor of epidermal growth factor receptor (EGFR) including but not limited to Cetuximab and Panitumimab. In some embodiments, the agent targeting a growth factor receptor is an inhibitor of insulin-like growth factor I (IGF-1) receptor (IGFI R) such as CP-751871. In other embodiments, the method further comprises surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, viral therapy, RNA therapy, immunotherapy, nanotherapy or a combination thereof. [0057] In some embodiments, the treatment comprises a treatment cycle of at least I I days, i.e. about 11 to about 30 days in length, wherein on from 1 to 10 separate days of the cycle, the patient receives about I to about 100 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, on from I to 10 separate days of 19 the cycle, the patient receives about 1 to about 50 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, on from I to 10 separate days of the cycle, the patient receives about 1, 2, 3, 4, 6, 8 or 10, 12, 14, 16, 18 or 20 mg/kg of 4-iodo-3-nitrobenzamide. [0058] Some embodiment described herein provide a method of treating uterine cancer or endometrial cancer in a patient, comprising during a 21 day treatment cycle on days 1, 4, 8 and 11 of the cycle, administering to the patient about I to about 100 mg/kg of 4-iodo-3 nitrobenzamide or a molar equivalent of a metabolite thereof. In some embodiments, the 4 iodo-3-nitrobenzamide is administered orally or as a parenteral injection or infusion, or inhalation. [0059] Some embodiments described herein provide a method of treating uterine cancer or endometrial cancer in a patient, comprising: (a) establishing a treatment cycle of about 10 to about 30 days in length; (b) on from I to 10 separate days of the cycle, administering to the patient about 1 mg/kg to about 100 mg/kg of 4-iodo-3-nitrobenzamide, or a molar equivalent of a metabolite thereof. In some embodiments, the 4-iodo-3-nitrobenzamide is administered orally or as a parenteral injection or infusion, or inhalation. [0060] Some embodiments provided herein include a method of treating uterine cancer in a patient in need of such treatment, comprising: (a) obtaining a sample from the patient; (b) determining if the uterine cancer is recurrent, persistent or advanced; (e) if the testing indicates that the uterine cancer is recurrent, persistent or advanced, treating the patient with at least one PARP inhibitor; and (d) if the testing does not indicate that the patient has a uterine cancer that is recurrent, persistent or advanced, selecting a different treatment option. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a uterine tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor, In some embodiments, the clinical benefit rate is at least about 30%. In some embodiments, the PARP inhibitor is a PARP-1 inhibitor. In other embodiments, the PARP- 1 inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4-iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the sample is a tissue or bodily fluid sample. In some embodiments, the sample is a tumor sample, a blood sample, a blood plasma sample, a peritoneal fluid sample, an exudate or an effusion. In some embodiments, the uterine cancer is a metastatic uterine cancer. 20 [0061] Some embodiments provide a method of treating uterine cancer, endometrial cancer, or ovarian cancer in a patient, comprising: (a) testing a sample from the patient for PARP expression; and (b) if the PARP expression exceeds a predetermined level, administering to the patient at least one PARP inhibitor. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a uterine tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In some embodiments, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment without the PARP inhibitor. In some embodiments, the improvement of clinical benefit rate is at least about 30%. In some embodiments, the PARP inhibitor is a PARP- I inhibitor. In other embodiments, the PARP- 1 inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4 iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the uterine cancer is a metastatic uterine cancer. In some embodiments, the ovarian cancer is a metastatic ovarian cancer. 10062] Thus, embodiments provided herein comprise treating a patient with at least one of which is a PARP inhibitor, wherein the PARP inhibitor is optionally a PARP-l inhibitor. In some embodiments, one or more of these substances may be capable of being present in a variety of physical forms-e.g., free base, salts (especially pharmaceutically acceptable salts), hydrates, polymorphs, solvates, etc. Unless otherwise qualified herein, use of a chemical name is intended to encompass all physical forms of the named chemical, For example, recitation of 4-iodo-3 -nitrobenzamide, without further qualification, is intended to generically encompass the free base as well as all pharmaceutically acceptable salts, polymorphs, hydrates, etc. Where it is intended to limit the disclosure or claims to a particular physical form of a compound, this will be clear from the context of the passage or claim in which the reference to the compound appears. 100631 In some embodiments, the disclosure herein provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer in a patient, comprising administering to the patient a combination of at least one anti-tumor agent and at least one PARP inhibitor. In some embodiments, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In some embodiments, the PARP inhibitor is a benzamide or a metabolite thereof. In some embodiments, the benzamide is 4 iodo-3-nitrobenzamide or a metabolite thereof. In some embodiments, the anti-tumor agent is an antitumor alkylating agent, antitumor antimetabolite, antitumor antibiotics, plant-derived 21 antitumor agent, antitumor platinum complex, antitumor camptothecin derivative, antitumor tyrosine kinase inhibitor, monoclonal antibody, interferon, biological response modifier, hormonal anti-tumor agent, anti-tumor viral agent, angiogenesis inhibitor, differentiating agent, or other agent that exhibits anti-tumor activities, or a pharmaceutically acceptable salt thereof In some embodiments, the platinum complex is selected from the group consisting of cisplatin, carboplatin, oxaplatin and oxaliplatin. In some embodiments, the platinum complex is carboplatin. In some embodiments, the taxane is paclitaxel or docetaxel. In some embodiments, the taxane is paclitaxel. In some embodiments, the anti-tumor agent is an anti angiogenic agent, such as Avastin or a receptor tyrosine kinase inhibitor including but not limited to Sutent, Nexavar, Recentin, ABT-869, and Axitinib. In some embodiments, the anti tumor agent is a topoisomerase inhibitor including but not limited to irinotecan, topotecan, or camptothecin. In some embodiments, the anti-tumor agent is a taxane including but not limited to paclitaxel, docetaxel and Abraxane. In some embodiments, the anti-tumor agent is an agent targeting Her-2, e.g., Herceptin or lapatinib. In some embodiments, the anti-tumor agent is a hormone analog, for example, progesterone. In some embodiments, the anti-tumor agent is tamoxifen, a steroidal aromatase inhibitor, a non-steroidal aromatase inhibitor, or Fulvestrant. In some embodiments, the anti-tumor agent is an agent targeting a growth factor receptor. In some embodiments, such agent is an inhibitor of epidermal growth factor receptor (EGFR) including but not limited to Cetuximab and Panitumimab. In some embodiments, the agent targeting a growth factor receptor is an inhibitor of insulin-like growth factor 1 (IGF-1) receptor (IGFIR) such as CP-751871. In some embodiments, the cancer is a uterine cancer. In some embodiments, the cancer is advanced uterine carcinosarcoma, persistent uterine carcinosarcoma or recurrent uterine carcinosarcoma. In some embodiments, the cancer is endometrial cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is a metastatic ovarian cancer or uterine cancer. In some embodiments, the method comprises selecting a treatment cycle of at least I 1 days and: (a) on day I of the cycle, administering to the patient about 10-200 mg/in 2 of paclitaxel; (b) on day I of the cycle, administering to the patient about 10-400 mg/m 2 carboplatin; and (e) on day 1 and twice weekly throughout the cycle, administering to the patient about 1-100 mg/kg of 4-iodo-3-nitrobenzamide or a molar equivalent of a metabolite thereof. [0064] In some embodiments, the disclosure provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer in a patient, comprising: (a) obtaining a sample from the patient; (b) testing the sample to determine a level of PARP expression in the sample; (c) 22 determining whether the PARP expression exceeds a predetermined level, and if so, administering to the patient at least one taxane, at least one platinum complex and at least one PARP inhibitor. In some embodiments, the method further comprises optionally selecting a different treatment option if the PARP expression in the sample does not exceed the predetermined level. In some embodiments, the method optionally further comprises selecting a different treatment option if the PARP expression in the sample does not exceed the predetermined level. In some embodiments, the cancer is a uterine cancer. In some embodiments, the cancer is advanced uterine carcinosarcoma, persistent uterine carcinosarcoma or recurrent uterine careinosarcoma. In some embodiments, the cancer is an endometrial cancer. In some embodiments, the cancer is an ovarian cancer. In some embodiments, the cancer is a metastatic ovarian cancer. In some embodiments, the taxane is cisplatin, carboplatin, oxaplatin or oxaliplatin. In some embodiments, the taxane is paclitaxel. In some embodiments, the platinum complex is cisplatin or carboplatin. In some embodiments, the platinum complex is carboplatin. In some embodiments, the PARP inhibitor is a benzamide or a metabolite thereof. In some embodiments, the PARP inhibitor is 4-iodo-3-nitrobenzamide. In some embodiments, the sample is a tissue sample or a bodily fluid sample. [0065] In some embodiments, the present disclosure provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer in a patient, comprising during a 21 day treatment cycle: (a) on day I of the cycle, administering to the patient about 750 mg/m 2 of paclitaxel; (b) on day 1 of the cycle, administering to the patient about 10-400 mg/n 2 of carboplatin; and (c) on day I of the cycle, and twice weekly thereafter, administering to the patient about 1 -100 mg/kg of 4-iodo-3-nitrobenzamide. In some embodiments, the paclitaxel is administered as an intravenous infusion. In some embodiments, the carboplatin is administered as an intravenous infusion. In some embodiments, the 4-iodo-3.-nitrobenzamide is administered orally or as a parenteral injection or infusion, or inhalation. In some embodiments, the cancer is a uterine cancer selected from advanced uterine carcinosarcoma, persistent uterine carcinosarcoma and recurrent uterine carcinosarcoma. In some embodiments, the cancer is ovarian cancer. [0066] Some embodiments described herein provide a method of treating uterine cancer, endometrial cancer, or ovarian cancer in a patient, comprising: (a) establishing a treatment cycle of about 10 to about 30 days in length; (b) on from 1 to 5 separate days of the cycle, administering to the patient about 100 to about 2000 mg/m 2 of paclitaxel by intravenous infusion over about 10 to about 300 minutes; (c) on from I to 5 separate days of the cycle, 23 administering to the patient about 10-400 mg/m 2 of carboplatin by intravenous infusion over about 10 to about 300 minutes; and (d) on from I to 10 separate days of the cycle, administering to the patient about 1 mg/kg to about 8 mg/kg of 4-iodo-3-nitrobenzamide over about 10 to about 300 minutes. 10067] Some embodiments described herein provide a method of treating uterine cancer in a patient in need of such treatment, comprising: (a) testing a uterine tumor sample from the patient to determine at least one of the following: (i) whether the uterine cancer is advanced; (ii) whether the uterine cancer is persistent; (iii) whether the uterine cancer is recurrent; (b) if the testing indicates that the uterine cancer is advance, persistent or recurrent, treating the patient with a combination of therapeutic agents, wherein the therapeutic agents include at least one anti-tumor agent and at least one PARP inhibitor. In some embodiments, the at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a uterine tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, or stable disease. In some embodiments, the PARP inhibitor is a benzamide or a metabolite thereof In some embodiments, the benzamide is 4-iodo-3 nitrobenzamide or a metabolite thereof In some embodiments, the platinum complex is selected from the group consisting of cisplatin, carboplatin, oxaplatin and oxaliplatin. In some embodiments, the platinum complex is carboplatin. In some embodiments, the taxane is paclitaxel or docetaxel. In some embodiments, the taxane is paclitaxel. In some embodiments, the cancer is an advanced carcinosarcoma, a persistent carcinosarcoma or a recurrent carcinosarcoma. In some embodiments, the cancer is an endometrial cancer. 100681 In some embodiments, the method comprises treating a patient with at least three chemically distinct substances, one of which is a taxane (e.g., paclitaxel or docetaxel), one of which is a platinum-containing complex (e.g., cisplatin or carboplatin or cisplatin) and one of which is a PARP inhibitor (e.g., 4-iodo-3-nitrobenzamide or a metabolite thereof). In some embodiments, one or more of these substances may be capable of being present in a variety of physical forms-e.g., free base, salts (especially pharmaceutically acceptable salts), hydrates, polymorphs, solvates, or metabolites, etc. Unless otherwise qualified herein, use of a chemical name is intended to encompass all physical forms of the named chemical. For example, recitation of 4-iodo-3-nitrobenzamide, without further qualification, is intended to generically encompass the free base as well as all pharmaceutically acceptable salts, polymorphs, hydrates, and metabolites thereof. Where it is intended to limit the disclosure or claims to a particular physical form of a compound, this will be clear from the context of the passage or claim in which the reference to the compound appears. 24 Anti-tumor agents 10069] Anti-tumor agents that may be used in the present invention include but are not limited to antitumor alkylating agents, antitumor antimetabolites, antitumor antibiotics, plant derived antitumor agents, antitumor platinum-complex compounds, antitumor camptothecin derivatives, antitumor tyrosine kinase inhibitors, anti-tumor viral agent, monoclonal antibodies, interferons, biological response modifiers, and other agents that exhibit anti-tumor activities, or a pharmaceutically acceptable salt thereof. [0070] In some embodiments, the anti-tumor agent is an alkylating agent. The term "alkylating agent" herein generally refers to an agent giving an alkyl group in the alkylation reaction in which a hydrogen atom of an organic compound is substituted with an alkyl group. Examples of anti-tumor alkylating agents include but are not limited to nitrogen mustard N-oxide, cyclophosphamide, ifosfamide, melphalan, busulfan, mitobronitol, carboquone, thiotepa, ranimustine, nimustine, temozolomide or carmustine. 10071] In some embodiments, the anti-tumor agent is an antimetabolite. The term "antimetabolite" used herein includes, in a broad sense, substances which disturb normal metabolism and substances which inhibit the electron transfer system to prevent the production of energy-rich intermediates, due to their structural or functional similarities to metabolites that are important for living organisms (such as vitamins, coenzymes, amino acids and saccharides). Examples of antimetabolites that have anti-tumor activities include but are not limited to methotrexate, 6-mercaptopurine riboside, mercaptopurine, 5 fluorouracil, tegafur, doxifluridine, carmofur, cytarabine, cytarabine ocfosfate, enocitabine, S-1, gemeitabine, fludarabine or pemetrexed disodium, and preferred are 5-fluorouracil, S-1, gemcitabine and the like. 100721 In some embodiments, the anti-tumor agent is an antitumor antibiotic. Examples of antitumor antibiotics include but are not limited to actinomycin D, doxorubicin, daunorubicin, neocarzinostatin, bleomycin, peplomycin, mitomycin C, aclarubicin, pirarubicin, epirubicin, zinostatin stimalamer, idarubicin, sirolimus or valrubicin. In some embodiments, the anti-tumor agent is a plant-derived antitumor agent. Examples of plant-derived antitumor agents include but are not limited to vincristine, vinblastine, vindesine, etoposide, sobuzoxane, docetaxel, paclitaxel and vinorelbine, and preferred are docetaxel and paclitaxel. [0073] In some embodiments, the anti-tumor agent is a camptothecin derivative that exhibits anti-tumor activities. Examples of anti-tumor camptothecin derivatives include but 25 are not limited to camptothecin, 10-hydroxycanptothecin, topotecan, irinotecan or 9 aminocamptothecin, with camptothecin, topotecan and irinotecan being preferred. Further, irinotecan is metabolized in vivo and exhibits antitumor effect as SN-38. The action mechanism and the activity of the camptothecin derivatives are believed to be virtually the same as those of camptothecin (e.g., Nitta, et al., Gan to Kagaku Ryoho, 14, 850-857 (1987)). [0074] In some embodiments, the anti-tumor agent is an organoplatinum compound or a platinum coordination compound having antitumor activity. The terms "organoplatinum compound," "platinum compound," or "platinum complex" and the like as used herein refer to a platinum-containing compound which provides platinum in ion form. Preferred organoplatinum compounds include but are not limited to cisplatin; cis diamminediaquoplatinum (11)-ion; chloro(diethylenetriamine)-platinum (II) chloride; dichloro(ethylenediamine)-platinum (II); diammine(1,1 -cyclobutanedicarboxylato) platinum (II) (carboplatin); spiroplatin; iproplatin; diammine(2-ethylmalonato)platinum (II); ethylenediaminemalonatoplatinum (II); aqua(1,2-diaminodicyclohexane)sulfatoplatinum (II); aqua(] ,2-diaminod icyclohexane)malonatoplatinum (II); (1,2 diaminocyclohexane)malonatoplatinum (II); (4-carboxyphthalato)(1,2-diaminocyclohexane) platinum (II); (1,2-diaminocyclohexane)-(isocitrato)platinum (II); (1,2 diaminocyclohexane)oxalatoplatinum (II); ormaplatin; tetraplatin; carboplatin, nedaplatin and oxaliplatin, and preferred is carboplatin or oxaliplatin. Further, other antitumor organoplatinum compounds mentioned in the specification are known and are commercially available and/or producible by a person having ordinary skill in the art by conventional techniques. 100751 In some embodiments, the anti-tumor agent is an antitumor tyrosine kinase inhibitor. The term "tyrosine kinase inhibitor" herein refers to a chemical substance inhibiting "tyrosine kinase" which transfers a &phosphate group of ATP to a hydroxyl group of a specific tyrosine in protein. Examples of anti-tumor tyrosine kinase inhibitors include but are not limited to gefitinib, imatinib, erlotinib, Sutent, Nexavar, Recentin, ABT-869, and Axitinib. [0076] In some embodiments, the anti-tumor agent is an antibody or a binding portion of an antibody that exhibits anti-tumor activity. In some embodiments, the anti-tumor agent is a monoclonal antibody. Examples thereof include but are not limited to abeiximab, adalimumab, alemtuzumab, basiliximab, bevacizumab, cetuximab, daclizumab, eculizumab, efalizumab, ibritumomab, tiuxetan, infliximab, muromonab-CD3, natal i zumab, omalizumab, 26 palivizumab, panitumumab, ranibizumab, gemtuzumab ozogamicin, rituximab, tositumomab, trastuzumab, or any antibody fragments specific for antigens. [0077] In some embodiments, the anti-tumor agent is an interferon. Such interferon has antitumor activity, and it is a glycoprotein which is produced and secreted by most animal cells upon viral infection. It has not only the effect of inhibiting viral growth but also various immune effector mechanisms including inhibition of growth of cells (in particular, tumor cells) and enhancement of the natural killer cell activity, thus being designated as one type of cytokine. Examples of anti-tumor interferons include but are not limited to interferon a, interferon a -2a, interferon a-2b, interferon P, interferon 7-la and interferon y-n1. 10078] In some embodiments, the anti-tumor agent is a biological response modifier. It is generally the generic term for substances or drugs for modifying the defense mechanisms of living organisms or biological responses such as survival, growth or differentiation of tissue cells in order to direct them to be useful for an individual against tumor, infection or other diseases. Examples of the biological response modifier include but are not limited to krestin, lentinan, sizofiran, picibanil and ubenimex. 100791 In some embodiments, the anti-tumor agents include but are not limited to mitoxantrone, L-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pentostatin, tretinoin, alefacept, darbepoetin alfa, anastrozole, exemestane, bicalutamide, leuprorelin, flutamide, fulvestrant, pegaptanib octasodium, denileukin diftitox, aldesleukin, thyrotropin alfa, arsenic trioxide, bortezornib, capecitabine, and goserelin. [0080] The above-described terms "antitumor alkylating agent", "antitumor antimetabolite", "antitumor antibiotic", "plant-derived antitumor agent", antitumorr platinum coordination compound", "antitumor camptothecin derivative", antitumorr tyrosine kinase inhibitor", "monoclonal antibody", "interferon", "biological response modifier" and "other antitumor agent" are all known and are either commercially available or producible by a person skilled in the art by methods known per se or by well-known or conventional methods. The process for preparation of gefitinib is described, for example, in U.S. Pat. No. 5,770,599; the process for preparation of cetuximab is described, for example, in WO 96/402 10; the process for preparation of bevacizumab is described, for example, in WO 94/10202; the process for preparation of oxaliplatin is described, for example, in U.S. Pat. Nos. 5,420,319 and 5,959,133; the process for preparation of gemcitabine is described, for example, in U.S. Pat. Nos. 5,434,254 and 5,223,608; and the process for preparation of camptothecin is described in U.S. Pat. Nos. 5,162,532, 5,247,089, 5,191,082, 5,200,524, 5,243,050 and 5,321,140; the process for preparation of irinotecan is described, for example, in U.S. Pat, 27 No, 4,604,463; the process for preparation of topotecan is described, for example, in U.S. Pat. No. 5,734,056; the process for preparation of temozolomide is described, for example, in JP B No. 4-5029; and the process for preparation of rituximab is described, for example, in JP W No. 2-503143. [00811 The above-mentioned antitumor alkylating agents are commercially available, as exemplified by the following: nitrogen mustard N-oxide from Mitsubishi Pharma Corp. as Nitrorin (tradename); cyclophosphamide from Shionogi & Co., Ltd. as Endoxan (tradename); ifosfamide from Shionogi & Co., Ltd. as Ifomide (tradename); melphalan from GlaxoSmithKline Corp. as Alkeran (tradename); busulfan from Takeda Pharmaceutical Co., Ltd. as Mablin (tradename); mitobronitol from Kyorin Pharmaceutical Co., Ltd, as Myebrol (tradename); carboquone from Sankyo Co., Ltd. as Esquinon (tradename); thiotepa from Sumitomo Pharmaceutical Co., Ltd. as Tespamin (tradename); ranimustine from Mitsubishi Pharma Corp. as Cymerin (tradename); nimustine from Sankyo Co., Ltd, as Nidran (tradename); temozolomide from Schering Corp. as Temodar (tradename); and carmustine from Guilford Pharmaceuticals Inc. as Gliadel Wafer (tradename). 10082] The above-mentioned antitumor antimetabolites are commercially available, as exemplified by the following: methotrexate from Takeda Pharmaceutical Co., Ltd. as Methotrexate (tradename); 6-mercaptopurine riboside from Aventis Corp. as Thioinosine (tradename); mercaptopurine from Takeda Pharmaceutical Co., Ltd. as Leukerin (tradename); 5-fluorouracil from Kyowa Hakko Kogyo Co., Ltd. as 5-FU (tradename); tegafur from Taiho Pharmaceutical Co., Ltd. as Futraful (tradename); doxyfluridine from Nippon Roche Co., Ltd. as Furutulon (tradename); carmofur from Yamanouchi Pharmaceutical Co., Ltd. as Yamafur (tradename); cytarabine from Nippon Shinyaku Co., Ltd. as Cylocide (tradename); cytarabine ocfosfatc from Nippon Kayaku Co., Ltd. as Strasid(tradename); enocitabine from Asahi Kasci Corp. as Sanrabin (tradename); S-1 from Taiho Pharmaceutical Co., lid, as TS-1 (tradename); gemcitabine from Eli Lilly & Co. as Gemzar (tradename); fludarabine from Nippon Schering Co., Ltd. as Fludara (tradename); and pemetrexed disodium from Eli Lilly & Co. as Alimta (tradename). 10083] The above-mentioned antitumor antibiotics are commercially available, as exemplified by the following: actinomycin D from Banyu Pharmaceutical Co., Ltd. as Cosmegen (tradename); doxorubicin from Kyowa Hakko Kogyo Co., Ltd. as adriacin (tradename); daunorubicin from Meiji Seika Kaisha Ltd. as Daunomycin; neocarzinostatin from Yamanouchi Pharmaceutical Co., Ltd. as Neocarzinostatin (tradename); bleomycin from Nippon Kayaku Co., Ltd. as Bleo (tradename); pepromycin from Nippon Kayaku Co, 28 Ltd. as Pepro (tradename); mitomycin C from Kyowa Hakko Kogyo Co., Ltd. as Mitomycin (tradename); aclarubicin from Yamanouchi Pharmaceutical Co., Ltd. as Aclacinon (tradename); pirarubicin from Nippon Kayaku Co., Ltd. as Pinorubicin (tradename); epirubicin from Pharmacia Corp. as Pharmorubicin (tradename); zinostatin stimalamer from Yamanouchi Pharmaceutical Co., Ltd. as Smanes (tradename); idarubicin from Pharmacia Corp. as Idamycin (tradename); sirolimus from Wyeth Corp. as Rapamune (tradename); and valrubicin from Anthra Pharmaceuticals Inc. as Valstar (tradename). [0084] The above-mentioned plant-derived antitumor agents are commercially available, as exemplified by the following: vincristine from Shionogi & Co., Ltd. as Oncovin (tradename); vinblastine from Kyorin Pharmaceutical Co., Ltd. as Vinblastine (tradename); vindesine from Shionogi & Co., Ltd. as Fildesin (tradename); etoposide from Nippon Kayaku Co., Ltd. as Lastet (tradename); sobuzoxane from Zenyaku Kogyo Co., Ltd. as Perazolin (tradename); docetaxel from Aventis Corp. as Taxsotere (tradename); paclitaxel from Bristol-Myers Squibb Co. as Taxol (tradename); and vinorelbine from Kyowa Hakko Kogyo Co., Ltd. as Navelbine (tradename). [00851 The above-mentioned antitumor platinum coordination compounds are commercially available, as exemplified by the following: cisplatin from Nippon Kayaku Co., Ltd. as Randa (tradename); carboplatin from Bristol-Myers Squibb Co. as Paraplatin (tradename); nedaplatin from Shionogi & Co., Ltd. as Aqupla (tradename); and oxaliplatin from Sanofi-Synthelabo Co. as Eloxatin (tradename). [0086] The above-mentioned antitumor camptothecin derivatives are commercially available, as exemplified by the following: irinotecan from Yakult Honsha Co., Ltd. as Campto (tradename); topotecan from GlaxoSmithKline Corp. as Hycamtin (tradename); and camptothecin from Aldrich Chemical Co., Inc., U.S.A. 10087] The above-mentioned antitumor tyrosine kinase inhibitors are commercially available, as exemplified by the following: gefitinib from AstraZeneca Corp. as Iressa (tradename); imatinib from Novartis AG as Gleevec (tradename); and erlotinib from OSI Pharmaceuticals Inc. as Tarceva (tradename). [0088] The above-mentioned monoclonal antibodies are commercially available, as exemplified by the following: cetuximab from Bristol-Myers Squibb Co. as Erbitux (tradename); bevacizumab from Genentech, Inc. as Avastin (tradename); rituximab from Biogen Idec Inc. as Rituxan (tradename); alemtuzumab from Berlex Inc. as Campath (tradename); and trastuzumab from Chugai Pharmaceutical Co., Ltd. as Herceptin (tradename). 29 [0089] The above-mentioned interferons are commercially available, as exemplified by the following: interferon a from Sumitomo Pharmaceutical Co., Ltd. as Sumiferon (tradename); interferon a-2a from Takeda Pharmaceutical Co., Ltd. as Canferon-A (tradename); interferon a-2b from Schering-Plough Corp. as Intron A (tradename); interferon P from Mochida Pharmaceutical Co., Ltd. as IFN.beta. (tradename); interferon y-la from Shionogi & Co., Ltd. as Imunomax-y (tradename); and interferon T-nl from Otsuka Pharmaceutical Co., Ltd. as Ogamma (tradename). [0090] The above-mentioned biological response modifiers are commercially available, as exemplified by the following: krestin from Sankyo Co., Ltd. as krestin (tradename); lentinan from Aventis Corp. as Lentinan (tradename); sizofiran from Kaken Seiyaku Co., Ltd. as Sonifiran (tradename); picibanil from Chugai Pharmaceutical Co., Ltd. as Picibanil (tradename); and ubenimex from Nippon Kayaku Co., Ltd. as Bestatin (tradename). [00911 The above-mentioned other antitumor agents are commercially available, as exemplified by the following: mitoxantrone from Wyeth Lederle Japan, Ltd. as Novantrone (tradename); L-asparaginase from Kyowa Hakko Kogyo Co., Ltd. as Leunase (tradename); procarbazine from Nippon Roche Co., Ltd. as Natulan (tradename); dacarbazine from Kyowa lakko Kogyo Co., Ltd, as Dacarbazine (tradename); hydroxycarbamide from Bristol-Myers Squibb Co. as Hydrea (tradename); pentostatin from Kagaku Oyobi Kessei Ryoho Kenkyusho as Coforin (tradename); tretinoin from Nippon Roche Co., Ltd. As Vesanoid (tradename); alefacept from Biogen Idec Inc. as Amevive (tradename); darbepoetin alfa from Amgen Inc. as Aranesp (tradename); anastrozole from AstraZeneca Corp. as Arimidex (tradename); exenestane from Pfizer Inc. as Aromasin (tradename); bicalutlamide from AstraZeneca Corp. as Casodex (tradename); leuprorelin from Takeda Pharmaceutical Co., Ltd. as Leuplin (tradename); flutamide from Schering-Plough Corp. as Eu ilexin (tradename); fulvestrant from AstraZeneca Corp. as Faslodex (tradename); pegaptanib octasodium from Gilead Sciences, Inc. as Macugen (tradename); denileukin diftitox from Ligand Pharmaceuticals Inc. as Ontak (tradename); aldesleukin from Chiron Corp. as Proleukin (tradename); thyrotropin alfa from Genzyme Corp. as Thyrogen (tradename); arsenic trioxide from Cell Therapeutics, Inc. as Trisenox (tradename); bortezomib from Millennium Pharmaceuticals, Inc. as Velcade (tradename); capecitabine from Hoffinann-La Roche, Ltd. as Xeloda (tradename); and goserelin from AstraZeneca Corp. as Zoladex (tradename). The term "antitumor agent" as used in the specification includes the above-described antitumor alkylating agent, antitumor antimetabolite, antitumor antibiotic, plant-derived antitumor agent, antitunor platinum coordination compound, antitumor camptothecin derivative, 30 antitumor tyrosine kinase inhibitor, monoclonal antibody, interferon, biological response modifier, and other antitumor agents. [0092] Other anti-tumor agents or anti-neoplastic agents can be used in combination with benzopyrone compounds. Such suitable anti-tumor agents or anti-neoplastic agents include, but are not limited to, 13-cis-Retinoic Acid, 2-CdA, 2-Chlorodeoxyadenosine, 5-Azacitidine, 5-Fluorouracil, 5-FU, 6-Mercaptopurine, 6-MP, 6-TG, 6-Thioguanine, Abraxane, Accutane, Actinomycin-D, Adriamycin, Adrucil, Agrylin, Ala-Cort, Aldesleukin, Alemtuzumab, ALIMTA, Alitretinoin, Alkaban-AQ, Alkeran, All-transretinoic Acid, Alpha Interferon, Altretamine, Amethopterin, Amifostine, Aminoglutethimide, Anagrelide, Anandron, Anastrozole, Arabinosylcytosine, Ara-C, Aranesp, Aredia, Arimidex, Aromasin, Arranon, Arsenic Trioxide, Asparaginase, ATRA, Avastin, Azacitidine, BCG, BCNU, Bendamustine, Bevacizumab, Bexarotene, BEXXAR, Bicalutamide, BiCNU, Blenoxane, Bleomycin, Bortezomib, Busulfan, Busulfex, C225, Calcium Leucovorin, Campath, Camptosar, Camptothecin-1 1, Capecitabine, Carac, Carboplatin, Carmustine, Carmustine Wafer, Casodex, CC-5013, CCI-779, CCNU, CDDP, CceNU, Cerubidine, Cetuximab, Chlorambucil, Cisplatin, Citrovorum Factor, Cladribine, Cortisone, Cosmegen, CPT- 11, Cyclophosphamide, Cytadren, Cytarabine, Cytarabine Liposomal, Cytosar-U, Cytoxan, Dacarbazine, Dacogen, Dactinomycin, Darbepoetin Alfa, Dasatinib, Daunomycin, Daunorubicin, Daunorubicin Hydrochloride, Daunorubicin Liposomal, DaunoXome, Decadron, Decitabine, Delta-Cortef, Deltasone, Denileukin Diftitox, DepoCytTM, Dexamethasone, Dexamethasone Acetate, Dexamethasone Sodium Phosphate, Dexasone, Dexrazoxane, DH AD, DIC, Diodex, Docetaxel, Doxil, Doxorubicin, Doxorubicin Liposomal, DroxiaTM, DTIC, DTIC-Dome, Duralone, Efudex, Eligard, Ellence, Eloxatin, Elspar, Emcyt, Epirubicin, Epoetin Alfa, Erbitux, Erlotinib, Erwinia L-asparaginase, Estramustine, Ethyol, Etopophos, Etoposide, Etoposide Phosphate, Eulexin, Evista, Exemestane, Fareston, Faslodex, Femara, Filgrastim, Floxuridine, Fludara, Fludarabine, Fluoroplex, Fluorouracil, Fluorouracil (cream), Fluoxymesterone, Filutamide, Folinic Acid, FUDR , Fulvestrant, G CSF, Gefitinib, Gemcitabine, Gemtuzumab ozogamicin, Gemzar & Gemzar Side Effects Chemotherapy Drugs, Gleevec, Gliadel Wafer, GM-CSF, Goserelin, Granulocyte - Colony Stimulating Factor, Granulocyte Macrophage Colony Stimulating Factor, Halotestin, Herceptin, lexadrol, Ilexalen, Hexamethylmelamine, 1MM, Hycamtin, Hydrea, Hydrocort Acetate, Hydrocortisone, Hydrocortisone Sodium Phosphate, Hydrocorti sone Sodium Succinate, Hydrocortone Phosphate, Hydroxyurea, Ibritumomab, Ibritumomab Tiuxetan, Idamycin, Idarubicin, Ifex , IFN-alpha, Ifosfamide, IL-1 1, IL-2, Imatinib mesylate, Imidazole 3] Carboxamide, Interferon alfa, Interferon Alfa-2b (PEG Conjugate), Interleukin - 2, Interleukin-1 1, Intron A (interferon alfa-2b), Iressa, Irinotecan, Isotretinoin, Ixabepilone, Ixempra, Kidrolase (t), Lanacort, Lapatinib, L-asparaginase, LCR, Lenalidomide, Letrozole, Leucovorin, Leukeran, Leukine, Leuprolide, Leurocristine, Leustatin, Liposomal Ara-C, Liquid Pred, Lomustine, L-PAM, L-Sarcolysin, Lupron, Lupron Depot, Matulane, Maxidex, Mechlorethamine, Mechlorethamine Hydrochloride, Medralone, Medrol, Megace, Megestrol, Megestrol Acetate, Melphalan, Mercaptopurine, Mesna, Mesnex, Methotrexate, Methotrexate Sodium, Methylprednisolone, Meticorten, Mitomycin, Mitomycin-C, Mitoxantrone, M Prednisol, MTC, MTX, Mustargen, Mustine, Mutamycin, Myleran, Mylocel, Mylotarg, Navelbine, Nelarabine, Neosar, Neulasta, Neurnega, Neupogen, Nexavar, Nilandron, Nilutarmide, Nipent, Nitrogen Mustard, Novaldex, Novantrone, Octreotide, Octreotide acetate, Oncospar, Oncovin, Ontak, Onxal, Oprevelkin, Orapred, Orasone, Oxaliplatin, Paclitaxel, Paclitaxel Protein-bound, Pamidronate, Panitumumab, Panretin, Paraplatin, Pediapred, PEG Interferon, Pegaspargase, Pegfilgrastim, PEG-INTRON, PEG-L asparaginase, PEMETREXED, Pentostatin, Phenylalanine Mustard, Platinol, Platinol-AQ, Prednisolone, Prednisone, Prelone, Procarbazine, PROCRIT, Proleukin, Prolifeprospan 20 with Carmustine Implant, Purinethol, Raloxifene, Revlimid, Rheumatrex, Rituxan, Rituximab, Roferon-A (Interferon Alfa-2a), Rubex, Rubidomycin hydrochloride, Sandostatin, Sandostatin LAR, Sargramostim, Solu-Cortef, Solu-Medrol, Sorafenib, SPRYCEL, STI-571, Streptozocin, SU 11248, Sunitinib, Sutent, Tamoxifen, Tarceva, Targretin, Taxol, Taxotere, Temodar, Temozolomide, Temsirolimus, Teniposide, TESPA, Thalidomide, Thalomid, TheraCys, Thioguanine, Thioguanine Tabloid, Thiophosphoamide, Thioplex, Thi otepa, TICE, Toposar, Topotecan, Toremifene, Torisel, Tositumomab, Trastuzumab, Tretinoin, Trexall"M, Trisenox, TSPA, TYKERB, VCR, Vectibix, Vectibix, Velban, Velcade, VePesid, Vesanoid, Viadur, Vidaza, Vinblastine, Vinblastine Sulfate, Vincasar Pfs, Vincristine, Vinorelbine, Vinorelbine tartrate, VLB, VM-26, Vorinostat, VP-16, Vumon, Xeloda, Zanosar, Zevalin, Zinecard, Zoladex, Zoledronic acid, Zolinza, Zometa. Antimetabolites [0093] Antimetabolites are drugs that interfere with normal cellular metabolic processes. Since cancer cells are rapidly replicating, interference with cellular metabolism affects cancer cells to a greater extent than host cells, Gemcitabine ( 4 -amino-1-[3,3-difluoro-4-hydroxy-5 (hydroxymethyl) tetrahydrofuran-2-yl] -1 H-pyrinidin-2-one; marketed as GEMZAR* by Eli 32 Lilly and Company) is a nucleoside analog, which interferes with cellular division by blocking DNA synthesis, thus resulting in cell death, apparently through an apoptotic mechanism. The dosage of gemcitabine may be adjusted to the particular patient. In adults, the dosage of gemcitabine, when used in combination with a platinum agent and a PARP inhibitor, will be in the range of about 100 mg/mn 2 to about 5000 mg/m 2 , in the range of about 100 mg/im 2 to about 2000 mg/im 2 , in the range of about 750 to about 1500 mg/m2, about 900 to about 1400 mg/m 2 or about 1250 mg/n 2 . The dimensions mg/n 2 refer to the amount of gemcitabine in milligrams (mg) per unit surface area of the patient in square meters (M) . Gemcitabine may be administered by intravenous (IV) infusion, e.g., over a period of about 10 to about 300 minutes, about 15 to about 180 minutes, about 20 to about 60 minutes or about 10 minutes. The term "about" in this context indicates the normal usage of approximately; and in some embodiments indicates a tolerance of 10% or -I5%. Taxanes {0094] Taxanes are drugs that are derived from the twigs, needles and bark of Pacific yew tress, Taxus brevifolia. In particular paclitaxel may be derived from 10-deacetylbaccatin through known synthetic methods. Taxanes such as paclitaxel and its derivative docetaxel have demonstrated antitumor activity in a variety of tumor types. The taxanes interfere with normal function of microtubule growth by hyperstabilizing their structure, thereby destroying the cell's ability to use its cytoskeleton in a normal manner. Specifically, the taxanes bind to the 0 subunit of tubulin, which is the building block of microtubules. The resulting taxane/tubulin complex cannot disassemble, which results in aberrant cell function and eventual cell death. Paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-inhibiting protein called Bcl-2 (B-cell leukemia 2), thereby preventing Bel-2 from inhibiting apoptosis. Thus paclitaxel has proven to be an effective treatment for various cancers, as it down-regulates cell division by interrupting normal cytoskeletal rearrangement during cell division and it induces apoptosis via the anti-Bel-2 mechanism. [0095] The dosage of paclitaxel may vary depending upon the height, weight, physical condition, tumor size and progression state, etc. In some embodiments, the dosage of paclitaxel will be in the range of about 10 to about 2000 mg/n 2 , about 10 to about 200 mg/m 2 or about 100 to about 175 mg/n. In some embodiments, the paclitaxel will be administered over a period of up to about 10 hours, up to about 8 hours or up to about 6 hours. The term 33 "about" in this context indicates the normal usage of approximately; and in some embodiments indicates a tolerance of± 10% or ± 5%. 10096] Examples of taxanes include but are not limited to docetaxel, paclitaxel, and Abraxane. Platinum complexes [0097] Platinum complexes are pharmaceutical compositions used to treat cancer, which contain at least one platinum center complexed with at least one organic group. Carboplatin ((SP-4-2)-Diammine [1,1 -cyclobutanedicarboxylato(2-)-0,O' platinum), like cisplatin and oxaliplatin, is a DNA alkylating agent. The dosage of a platinum compound, e.g., carboplatin, is determined by calculating the area under the blood plasma concentration versus time curve (AUC) in mg/mLeminute by methods known to those skilled in the cancer chemotherapy art, taking into account the patient's renal activity estimated by measuring creatinine clearance or glomerular filtration rate. In some embodiments, the dosage of carboplatin for combination treatment along with an antimetabolite (e.g., gemcitabine) and a PARP inhibitor (e.g., 4-iodo-3-nitrobenzamide) is calculated to provide an AUC of about 0.1 6 mg/ml-min, about 1-3 mg/ml'min, about 1.5 to about 2.5 mg/ml-min, about 1.75 to about 2.25 mg/ml-min or about 2 mg/ml-min. (AUC 2, for example, is shorthand for 2 mg/mleminute). Alternatively, the dosage of platinum compound, e.g., carboplatin, is calculated based on the patient's body surface area. In some embodiments, a suitable dose of carboplatin is about 10 to about 400 mg/m2, e.g., about 360 mg/m 2 . Platinum complexes, such as carboplatin, are normally administered intravenously (IV) over a period of about 10 to about 300 minutes, about 30 to about 180 minutes, about 45 to about 120 minutes or about 60 minutes. In this context, the term "about" has its normal meaning of approximately. In some embodiments, about means ±10% or ±5%. Topoisomerase inhibitors [00981 In some embodiments, the methods of the invention may comprise administering to a patient with uterine cancer or ovarian cancer an effective amount of a PARP inhibitor in combination with a topoisomerase inhibitor, for example, irinotecan and topotecan. [0099] Topoisomerase inhibitors are agents designed to interfere with the action of topoisomerase enzymes (topoisomerase I and II), which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of 34 DNA strands during the normal cell cycle. Topoisomerases have become popular targets for cancer chemotherapy treatments. It is thought that topoisomerase inhibitors block the ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently lead to apoptosis and cell death. Topoisomerase inhibitors are often divided according to which type of enzyme it inhibits. Topoisomerase I, the type of topoisomerase most often found in eukaryotes, is targeted by topotecan, irinotecan, lurtotecan and exatecan, each of which is commercially available. Topotecan is available from GlaxoSmithKline under the trade name Hycamtim*. Irinotecan is available from Pfizer under the trade name Camptosar*. Lurtotecan may be obtained as a liposomal formulation from Gilead Sciences Inc. Topoisomerase inhibitors may be administered at an effective dose. In some embodiments an effective dose for treatment of a human will be in the range of about 0.01 to about 10 mg/m2/day. The treatment may be repeated on a daily, bi-weekly, semi-weekly, weekly, or monthly basis. In some embodiments, a treatment period may be followed by a rest period of from one day to several days, or from one to several weeks. In combination with a PARP-1 inhibitor, the PARP- 1 inhibitor and the topoisomerase inhibitor may be dosed on the same day or may be dosed on separate days. [0100] Compounds that target type I topoisomerase are split into two main classes: topoisomerase poisons, which target the topoisomerase-DNA complex, and topoisomerase inhibitors, which disrupt catalytic turnover. Topo II poisons include but are not limited to eukaryotic type II topoisomerase inhibitors (topo II): amsacrine, etoposide, etoposide phosphate, teniposide, amrubicin and doxorubicin. These drugs are anti-cancer therapies. Examples of topoisomerase inhibitors include ICRF-193. These inhibitors target the N terminal ATPase domain of topo II and prevent topo II from turning over. The structure of this compound bound to the ATPase domain has been solved by Classen (Proceedings of the National Academy of Science, 2004) showing that the drug binds in a non-competitive manner and locks down the dimerization of the ATPase domain. Anti-angiogenic agents [0101] In some embodiments, the methods of the invention may comprise administering to a patient with uterine, endometrial, or ovarian cancer an effective amount of a PARP inhibitor in combination with an anti-angiogenic agent. 35 101021 An angiogenesis inhibitor is a substance that inhibits angiogenesis (the growth of new blood vessels). Every solid tumor (in contrast to leukemia) needs to generate blood vessels to keep it alive once it reaches a certain size. Tumors can grow only if they form new blood vessels. Usually, blood vessels are not built elsewhere in an adult body unless tissue repair is actively in process. The angiostatic agent endostatin and related chemicals can suppress the building of blood vessels, preventing the cancer from growing indefinitely. In tests with patients, the tumor became inactive and stayed that way even after the endostatin treatment is finished. The treatment has very few side effects but appears to have very limited selectivity. Other angiostatic agents such as thalidomide and natural plant-based substances are being actively investigated. [0103] Known inhibitors include the drug bevacizumab (Avastin), which binds vascular endothelial growth factor (VEGF), inhibiting its binding to the receptors that promote angiogenesis. Other anti-angiogenic agents include but are not limited to carboxyamidotriazole, TNF-470, CM101, IFN-alpha, IL-12, platelet factor-4, suramin, SU5416, thrombospondin, angiostatic steroids + heparin, cartilage-derived angiogenesis inhibitory factor, matrix metalloproteinase inhibitors, angiostatin, endostatin, 2 methoxyestradiol, tecogalan, thrombospondin, prolactin, -vp33 inhibitors and linomide. Her-2 targeted therapy [01041 In some embodiments, the methods of the invention may comprise administering to a patient with HER2-positive uterine, endometrial, or ovarian cancer an effective amount of a PARP inhibitor in combination with Herceptin. 10105] Her-2 overexpression has been found in ovarian carcinomas and HER2 overexpression and amplification is associated with advanced ovarian cancer (AOC) (Hellstrbm et al., Cancer Research 61, 2420-2423, March 15, 2001). Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease (Berchuck A, et al., Am J Obstet Gynecol. 1991 Jan;164(l Pt 1):15-21). Herceptin may be used for the adj uvant treatment of I IER2-overexpressing, uterine, endometrial, or ovarian cancers. Herceptin can be used several different ways: as part of a treatment regimen including doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline-based therapy. Herceptin in combination with paclitaxel is approved for the first-line treatment of HER2 overexpressing uterine, endometrial, or ovarian cancers. HTerceptin as a single agent is 36 approved for treatment of HER2-overexpressing uterine, endometrial, or ovarian cancer in patients who have received one or more chemotherapy regimens for metastatic disease. [0106] Lapatinib or lapatinib ditosylate is an orally active chemotherapeutic drug treatment for solid tumours such as breast cancer. During development it was known as small molecule GW572016. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by preventing them from dividing. Giving lapatinib together with topotecan may have enhanced anti-tumor efficacy. Hormone therapy [0107] In some embodiments, the methods of the invention may comprise administering to a patient with uterine, endometrial, or ovarian cancer an effective amount of a PARP inhibitor in combination with hormone therapy. [0108] Treatment for uterine cancer depends on the stage of the disease and the overall health of the patient. Removal of the tumor (surgical resection) is the primary treatment. Radiation therapy, hormone therapy, and/or chemotherapy may be used as adjuvant treatment (i.e., in addition to surgery) in patients with metastatic or recurrent disease. [0109] H-ormone therapy is used to treat metastatic or recurrent endometrial cancer. It also may be used to treat patients who are unable to undergo surgery or radiation. Prior to treatment, a hormone receptor test may be performed to determine if the endometrial tissue contains these proteins. Hormone therapy usually involves a synthetic type of progesterone in pill form. Estrogen can cause the growth of ovarian epithelial cancer cells. Thus, hormone therapy may be used to treat ovarian cancer. Tamoxifen-Hormone antagonist [0110] Tamoxifen (marketed as Nolvadex) slows or stops the growth of cancer cells present in the body. Tamoxifen is a type of drug called a selective estrogen-receptor modulator (SERM). It functions as an anti-estrogen. As tamoxifen may have stabilized rapidly advancing recurrent ovarian cancer, its role in the primary treatment of ovarian cancer in combination with cytotoxic chemotherapy should be considered. 10111] Steroidal and non-steroidal aromatase inhibitor. Aromatase inhibitors (AI) are a class of drugs used in the treatment of ovarian cancer in postmenopausal women that block the aromatase enzyme. Aromatase inhibitors lower the amount of estrogen in post 37 menopausal women who have hormone-receptor-positive ovarian cancer. With less estrogen in the body, the hormone receptors receive fewer growth signals, and cancer growth can be slowed down or stopped. [0112] Aromatase inhibitor medications include Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole). Each is taken by pill once a day, for up to five years. But for women with advanced (metastatic) disease, the medicine is continued as long as it is working well. [01131 Als are categorized into two types: irreversible steroidal inhibitors such as exemestane that form a permanent bond with the aromatase enzyme complex; and non steroidal inhibitors (such as anastrozole, letrozole) that inhibit the enzyme by reversible competition. [0114] Fulvestrant, also known as ICI 182,780, and "Faslodex" is a drug treatment of hormone receptor-positive ovarian cancer in postmenopausal women with disease progression following anti-estrogen therapy. Estrogen can cause the growth of ovarian epithelial cancer cells. Fulvestrant is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. It is administered as a once-monthly injection. Targeted therapy [0115] In some embodiments, the methods of the invention may comprise administering to a patient with uterine, endometrial, or ovarian cancer an effective amount of a PARP inhibitor in combination with an inhibitor targeting a growth factor receptor including but not limited to epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R). [01161 EGFR is overexpressed in the cells of certain types of human carcinomas including but not limited to lung, breast, uterine, endometrial, and ovarian cancers. EGFR over expression in ovarian cancer has been associated with poor prognosis. In addition, EGFR has been shown to be highly expressed in normal endometrium and overexpressed in endometrial cancer specimens, where it has been associated with a poor prognosis, Increased expression of EGFR may contribute to a drug resistant phenotype. The tyrosine kinase inhibitor ZD1839 (Iressa") has been studied as a single agent in a phase Il clinical trial (GOG 229C) of women with advanced endometrial cancer. Preliminary data analysis indicates that of 29 patients enrolled, 1 patient experienced a complete response and several others had stable disease at 6 38 months (Leslie, K.K.; et al., International Journal of Gynecological Cancer, Volume 15, Number 2, 2005, pp. 409-411(3). Examples of EGFR inhibitors include but are not limited to cetuximab, which is a chimeric monoclonal antibody given by intravenous injection for treatment of cancers including but not limited to metastatic colorectal cancer and head and neck cancer. Panitumimab is another example of EGFR inhibitor. It is a humanized monoclonal antibody against EGFR. Panitumimab has been shown to be beneficial and better than supportive care when used alone in patients with advanced colon cancer and is approved by the FDA for this use. [0117] Activation of the type 1 insulin-like growth factor receptor (IGFIR) promotes proliferation and inhibits apoptosis in a variety of cell types. One example of an IGF1R inhibitor is CP-751871. CP-751871 is a human monoclonal antibody that selectively binds to IGFIR, preventing IGF I from binding to the receptor and subsequent receptor autophosphorylation. Inhibition of IGFIR autophosphorylation may result in a reduction in receptor expression on tumor cells that express IGF1R, a reduction in the anti-apoptotic effect of IGF, and inhibition of tumor growth. IGFIR is a receptor tyrosine kinase expressed on most tumor cells and is involved in mitogenesis, angiogenesis, and tumor cell survival. PI3K/mTOR pathway [01181 Phosphatidylinositol-3-kinase (PI13K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-a. These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-IIER2 antibody trastuzumab. Akt and mTOR phosphorylation is also frequently detected in ovarian and endometrial cancer. The P13K pathway is, therefore, an attractive target for cancer therapy. NVP-BEZ235, a dual inhibitor of the P13K and the downstream mammalian target of rapamycin (mTOR) has been shown to have antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated pl 10-a (Violeta Serra, et al., Cancer Research 68, 8022-8030, October 1, 2008). Hsp 9 0 inhibitors [01191 These drugs target heat shock protein 90 (hsp90). Hsp9O is one of a class of chaperone proteins, whose normal job is to help other proteins acquire and maintain the shape required for those proteins to do their jobs. Chaperone proteins work by being in physical 39 contact with other proteins. Hsp90 can also enable cancer cells to survive and even thrive despite genetic defects which would normally cause such cells to die. Thus, blocking the function of HSP90 and related chaperone proteins may cause cancer cells to die, especially if blocking chaperone function is combined with other strategies to block cancer cell survival. Tubulin inhibitors [0120] Tubulins are the proteins that form microtubules, which are key components of the cellular cytoskeleton (structural network). Microtubules are necessary for cell division (mitosis), cell structure, transport, signaling and motility. Given their primary role in mitosis, microtubules have been an important target for anticancer drugs - often referred to as antimitotic drugs, tubulin inhibitors and microtubule targeting agents. These compounds bind to tubulin in microtubules and prevent cancer cell proliferation by interfering with the microtubule formation required for cell division. This interference blocks the cell cycle sequence, leading to apoptosis. Apoptosis inhibitors [01211 The inhibitors of apoptosis (lAP) are a family of functionally- and structurally related proteins, originally characterized in Baculovirus, which serve as endogenous inhibitors of apoptosis. The human IAP family consists of at least 6 members, and IAP homologs have been identified in numerous organisms. 10058-F4 is a c-Myc inhibitor that induces cell-cycle arrest and apoptosis. It is a cell-permeable thiazolidinone that specifically inhibits the c-Myc-Max interaction and prevents transactivation of c-Mye target gene expression. 10058-F4 inhibits tumor cell growth in a e-Mye-dependent manner both in vitro and in vivo. BI-6C9 is a tBid inhibitor and antiapoptotic. GNF-2 belongs to a new class of Bir-abl inhibitors. GNF-2 appears to bind to the myristoyl binding pocket, an allosteric site distant from the active site, stabilizing the inactive form of the kinase. It inhibits Ber-abl phosphorylation with an IC 5 O of 267 nM, but does not inhibit a panel of 63 other kinases, including native c-Abl, and shows complete lack of toxicity towards cells not expressing Ber Abl. GNF-2 shows great potential for a new class of inhibitor to study Ber-abl activity and to treat resistant Chronic myelogenous leukemia (CML), which is caused the Ber-Abl oncoprotein. Pifithrin-a is a reversible inhibitor of p53-mediated apoptosis and p53 dependent gene transcription such as cyclin G, p21/wafi, and mdm2 expression. Pifithrin-a enhances cell survival after genotoxic stress such as UV irradiation and treatment with 40 cytotoxic compounds including doxorubicin, etopoxide, paclitaxel, and cytosine-3-D arabinofuranoside. Pifithrin-a protects mice from lethal whole body y-irradiation without an increase in cancer incidence. PARP Inhibitors [0122] In some embodiments, the present invention provides a method of treating uterine cancer or ovarian cancer by administering to a subject in need thereof at least one PARP inhibitor. In other embodiments, the present invention provides a method of treating uterine cancer or ovarian cancer by administering to a subject in need thereof at least one PARP inhibitor in combination with at least one anti-tumor agent described herein. [0123] Not intending to be limited to any particular mechanism of action, the compounds described herein are believed to have anti-cancer properties due to the modulation of activity of a poly (ADP-ribose) polymerase (PARP). This mechanism of action is related to the ability of PARP inhibitors to bind PARP and decrease its activity. PARP catalyzes the conversion of r-nicotinamide adenine dinucleotide (NAD+) into nicotinamide and poly ADP-ribose (PAR). Both poly (ADP-ribose) and PARP have been linked to regulation of transcription, cell proliferation, genomic stability, and carcinogenesis (Bouchard V.J. et al., Experimental Hematology, Volume 31, Number 6, June 2003, pp. 446-454(9); Herceg Z.; Wang Z.-Q. Mutation Research! Fundamental anl Molecular Mechanisms q Mulagenesis, Volume 477, Number 1, 2 June 2001, pp. 97-110(14)). Poly(ADP-ribose) polymerase I (PARP1) is a key molecule in the repair of DNA single-strand breaks (SSBs) (de Murcia J, ct al., 1997, Proc Natl Acad Sci USA 94:7303-7307; Schreiber V, Danitzer F, Ame JC, de Murcia G (2006) Nat Rev Mol Cell Biol 7:517-528; Wang ZQ, et al., (1997) Genes Dev 11:2347-2358). Knockout of SSB repair by inhibition of PARPI function induces DNA double-strand breaks (DSBs) that can trigger synthetic lethality in cancer cells with defective homology- directed DSB repair (Bryant HIE, ct al., (2005) Nature 434:913 917; Farmer H, et al., (2005) Nature 434:917-921). [0124] BRCA1 and BRCA2 act as an integral component of the homologous recombination machinery (HR) (Narod SA, Foulkes WD (2004) Nat Rev Cancer 4:665-676; Gudmundsdottir K, Ashworth A (2006) Oncogene 25:5864-5874). [0125] Cells defective in BRCA I or BRCA2 have a defect in the repair of double-strand breaks (DSB) by the mechanism of homologous recombination (I IR) by gene conversion (Farmer H, et al., (2005) Nature 434:917-921; Narod SA, Foulkes WD (2004) Nat Rev 41 Cancer 4:665-676; Gudmundsdottir K, Ashworth A (2006) Oncogene 25:5864-5874; Helleday T, et al., (2008) Nat Rev Cancer 8:193-204). Deficiency in either of the breast cancer susceptibility proteins BRCAI or BRCA2 induces profound cellular sensitivity to the inhibition of poly(ADP-ribose) polymerase (PARP) activity, resulting in cell cycle arrest and apoptosis. It has been reported that the critical role of BRCA1 and BRCA2 in the repair of double-strand breaks by homologous recombination (HR) is the underlying reason for this sensitivity, and the deficiency of RAD51, RAD54, DSS1, RPA1, NBS1, ATR, ATM, CHIK, CHK2, FANCD2, FANCA, or FANCC induces such sensitivity (McCabe N. et al., Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition, Cancer research 2006, vol. 66, 8109-8115). It has been proposed that PARP 1 inhibition can be a specific therapy for cancers with defects in BRCA1/2 or other HR pathway components (Helleday T, et al., (2008) Nat Rev Cancer 8:193-204). Uterine tumors and ovarian tumors frequently harbor defects in DNA double strand break repair through homologous recombination (HR), such as BRCAI dysfunction (Rottenberg S, et al., Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84). [01261 Inhibiting the activity of a PARP molecule includes reducing the activity of these molecules. The term "inhibits" and its grammatical conjugations, such as "inhibitory," is not intended to require complete reduction in PARP activity. In some embodiments, such reduction is at least about 50%, at least about 75%, at least about 90%, or at least about 95% of the activity of the molecule in the absence of the inhibitory effect, e.g., in the absence of an inhibitor, such as a nitrobenzamide compound described herein. In some embodiments, inhibition refers to an observable or measurable reduction in activity. In some treatment scenarios, the inhibition is sufficient to produce a therapeutic and/or prophylactic benefit in the condition being treated. The phrase "does not inhibit" and its grammatical conjugations does not require a complete lack of effect on the activity. For example, it refers to situations where there is less than about 20%, less than about 10%, and preferably less than about 5% of reduction in PARP activity in the presence of an inhibitor such as a nitrobenzamide compound of the invention. 101271 Poly (ADP-ribose) polymerase (PARP) is an essential enzyme in DNA repair, thus playing a potential role in chemotherapy resistance. Targeting PARP potentially is thought to interrupt DNA repair, thereby enhancing taxane mediated-, antimetabo lite mediated-, topoisomerase inhibitor-mediated, and growth factor receptor inhibitor, e.g., IGF 1 R inhibitor mediated, and/or platinum complex mediated-DNA replication and/or repair in cancer cells. PARP inhibitors may also be highly active against ovarian cancer, uterine cancer, and 42 endometrial cancer with impaired function of BRCA 1 and BRCA2 or those patients with other DNA repair pathway defects. 101281 4-iodo-3-nitrobenzamide (BA) is a small molecule that acts on tumor cells without exerting toxic effects in normal cells. 4-iodo-3-nitrobenzamide is believed to achieve its anti neoplastic effect by inhibition of PARP. 4-iodo-3-nitrobenzamide is very lipophilic and distributes rapidly and widely into tissues, including the brain and cerebrospinal fluid (CSF). It is active against a broad range of cancer cells in vitro, including against drug resistant cell lines. The person skilled in the art will recognize that 4-iodo-3-nitrobenzamide may be administered in any pharmaceutically acceptable form, e.g., as a pharmaceutically acceptable salt, solvate, or complex. Additionally, as 4-iodo-3-nitrobenzamide is capable of tautomerizing in solution, the tautomeric form of 4-iodo-3-nitrobenzamide is intended to be embraced by the term BA (or the equivalent 4-iodo-3-nitrobenzamide), along with the salts, solvates or complexes. In some embodiments, 4-iodo-3-nitrobenzamide may be administered in combination with a cyclodextrin, such as hydroxypropylbetacyclodextrin. However, one skilled in the art will recognize that other active and inactive agents may be combined with 4 iodo-3-nitrobenzamide; and recitation of 4-iodo-3-nitrobenzamide will, unless otherwise stated, include all pharmaceutically acceptable forms thereof. [0129] Basal-like endometrial cancers have a high propensity to metastasize to the brain; and 4-iodo-3-nitrobenzamide is known to cross the blood-brain barrier. While not wishing to be bound by any particular theory, it is believed that 4-iodo-3-nitrobenzamide achieves its anti-neoplastic effect by inhibiting the function of PARP. In some embodiments, 4-iodo-3 nitrobenzamide can be used in the treatment of metastatic ovarian cancer. In some embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of metastatic titerine cancer. In some embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of metastatic endometrial cancer. In other embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with an anti-tumor agent. In some embodiments, the anti-tumor agent is an antimetabolite such as gemcitabine. In some embodiments, the anti-tumor agent is a platinum complex such as carboplatin. In some embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with a taxane such as paclitaxel. In other embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with an anti-angiogenic agent. In still other embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with a topoisomerase inhibitor such as irinotecan. In other 43 embodiments, 4-iodo-3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with hormone therapy. In still other embodiments, 4-iodo 3-nitrobenzamide can be used in the treatment of uterine, endometrial, or ovarian tumors in combination with a growth factor receptor inhibitor including but not limited to EGFR or IGFIR inhibitor. In some embodiments, the uterine, endometrial, or ovarian cancer is a metastatic cancer. [0130] The dosage of PARP inhibitor may vary depending upon the patient age, height, weight, overall health, etc. In some embodiments, the dosage of 4-iodo-3-nitrobenzamide is in the range of about 1 mg/kg to about 100 mg/kg, about 2 mg/kg to about 50 mg/kg, about 2 mg/kg, about 4 mg/kg, about 6 mg/kg, about 8 mg/kg, about 10 mg/kg, about 12 mg/kg, about 15 mg/kg, about 20 mg/kg, about 25 mg/kg, about 30 mg/kg, about 35 mg/kg, about 40 mg/kg, about 50 mg/kg, about 60 mg/kg, about 75 mg/kg, about 90 mg/kg, about 1 to about 25 mg/kg, about 2 to about 70 mg/kg, about 4 to about 100 mg, about 4 to about 25 mg/kg, about 4 to about 20 mg/kg, about 50 to about 100 mg/kg or about 25 to about 75 mg/kg. 4 iodo-3-nitrobenzamide may be administered intravenously, e.g., by IV infusion over about 10 to about 300 minutes, about 30 to about 180 minutes, about 45 to about 120 minutes or about 60 minutes (i.e. about 1 hour). In some embodiments, 4-iodo-3-nitrobenzamide may alternatively be administered orally. In this context, the term "about" has its normal meaning of approximately. In some embodiments, about means ±10% or ±5%. 101311 The synthesis of 4-iodo-3-nitrobenzamide (4-iodo-3-nitrobenzamide) is described in United States Patent No. 5,464,871, which is incorporated herein by reference in its entirety. 4-iodo-3-nitrobenzamide may be prepared in concentrations of 10 mg/mL and may be packaged in a convenient form, e.g., in 10 mL vials. 4-iodo-3-nitrobenzamide (BA) Metabolites [01321 As used herein "BA" means 4-iodo-3-nitrobenzamide; "BNO" means 4-iodo-3 nitrosobenzamide; "BNHOI" means 4-iodo-3-hydroxyaminobenzamide. [0133J Precursor compounds useful in the present invention are of Formula (1a) 44

C--NH

2 R5 R1 I ( a) R4 R2 R3 wherein Ri, R2, R 3 , R 4 , and R 5 are, independently selected from the group consisting of hydrogen, hydroxy, amino, nitro, iodo, (CI -C 6 ) alkyl, (CI -C 6 ) alkoxy, (C 3

-C

7 ) cycloalkyl, and phenyl, wherein at least two of the five R 1 , R 2 , R3, R4, and R5 substituents are always hydrogen, at least one of the five substituents are always nitro, and at least one substituent positioned adjacent to a nitro is always iodo, and pharmaceutically acceptable salts, solvates, isomers, tautomers, imetabolites, analogs, or pro-drugs thereof. Ri, R 2 , R3, R4, and RS can also be a halide such as chloro, fluoro, or bromo substituents. 10134] A preferred precursor compound of formula la is:

C-NH

2

NO

2 I 4-iodo-3-nitrobenzamide (13A) [01351 Some metabolites useful in the present invention are of the Formula (Ila): 0

C-NH

2 R,, R, (Ila) R4 R2 R3 wherein either: (1) at least one of R 1 , R2, R3, R 1 , and Rs substituent is always a sulfur containing substituent, and the remaining substituents RI, R 2 , R 3 , R4, and Rs are 45 independently selected from the group consisting of hydrogen, hydroxy, amino, nitro, iodo, bromo, fluoro, chloro, (C -C 6 ) alkyl, (Ci -C 6 ) alkoxy, (C 3

-C

7 ) cycloalkyl, and phenyl, wherein at least two of the five R1, R2, R3, R 4 , and R5 substituents are always hydrogen; or (2) at least one of R1, R2, R3, R 4 , and R5 substituents is not a sulfur-containing substituent and at least one of the five substituents R1, R2, R3, R4, and R 5 is always iodo, and wherein said iodo is always adjacent to a R 1 , R 2 , R3, R 4 , or R5 group that is either a nitro, a nitroso, a hydroxyamino, hydroxy or an amino group; and pharmaceutically acceptable salts, solvates, isomers, tautomers, metabolites, analogs, or pro-drugs thereof. In some embodiments, the compounds of (2) are such that the iodo group is always adjacent to a R1, R2, R3, R4 or R5 group that is a nitroso, hydroxyamino, hydroxy or amino group. In some embodiments, the compounds of (2) are such that the iodo group is always adjacent to a R 1 , R2, R3, R4 or R5 group that is a nitroso, hydroxyamino, or amino group, 101361 The following compositions are preferred metabolite compounds, each represented by a chemical formula: HN 0

H

2 N NN M HN HN 0 0H HN HNH H o ~OH 0 OH Ho 0 H MS472 MS601 46

H

2 N O + N S 0 R, MS213 R6 is selected from a group consisting of hydrogen, alkyl(C-C8), alkoxy (Cr-C 8 ), isoquinolinones, indol es, thiazole, oxazole, oxadiazole, thiophene, or phenyl.

H

2 N 0 N 0 S 0 NH OOH MS328 0 OH 0 N H 2

NH

2 0 NH 2 HN HN OH

NH

2 s4 S MSis3 MS261 s MS182 47

H

2 N 0 H 2 N H 2 N 0 OH 1 01-0 /i N OH N MS263 MS276 MS278 OH O OH 0 0 CH OH HO 0 0 HO OH OH $ OH s HN 0 HN0 HN -INCH H2N HN MS63Sb MS635a Ho 0 Ho 0 O N O 0H NH 00 NHH NO1 NO, O N H MS471 MS414 H OH Ho H H 0 OH MS692 0 C1.0 10137] While not being limited to any one particular mechanism, the following provides an example for MS292 metabolism via a nitroreductase or glutathione conjugation mechanism: 48 Nitroreductase mechanism 0 NH 2 0 NH 2 0 NH 2 H20 20 N 0

NO

2 NADPH/1H' NADP+ NO 2 N NADPIIH/H' NADP* O NH 2 0 NH 2 H20 HIOH

NH

2 NO NADP* NADP1/11 H [0138] 4-iodo-3-nitrobenzanide glutathione conjugation and metabolism: 49 Gluathione conjugation and melabolisin O NH2 O NH2 0 Nil, 6hittalhione Trnspepidase NO2 NO, S S NO, 0 O~N0 Molecular Weight 292 03 HN H2N 0 BSI-201 HN HN Molecular Weight: 342.33 H2N HO O Peptidase HO 0 Molecular Weight: 47144 0 NH2 0 NH2 N-acetylransfrnase NO, NO2 S HSCoA CiICOSCoA 0 0 O HH OH CH Molecular Weighi 327 31 Molecular Weight: 285.28 10139] The present invention provides for the use of the aforesaid nitrobenzamide metabolite compounds for the treatment of ovarian cancer with a genetic defect in a BRCA gene, or a uterine cancer that is recurrent, advanced or persistent. [0140] It has been reported that nitrobenzamide metabolite compounds have selective cytotoxicity upon malignant cancer cells but not upon non-malignant cancer cells. See Rice et at., Proc. Natl. Acad. Sci. USA 89:7703-7707 (1992), incorporated herein in it entirety. In one embodiment, the nitrobenzamide metabolite compounds utilized in the methods of the present invention may exhibit more selective toxicity towards tumor cells than non-tumor cells. The metabolites according to the invention may thus be administered to a patient in need of such treatment in conjunction with chemotherapy with at least one taxane (e.g., paclitaxel or docetaxel) in addition to the at least one platinum complex (e.g., carboplatin, cisplatin, etc.) The dosage range for such metabolites may be in the range of about 0.0004 to about 0.5 mmol/kg (millimoles of metabolite per kilogram of patient body weight), which dosage corresponds, on a molar basis, to a range of about 0.1 to about 100 mg/kg of 4-iodo-3 nitrobenzamide. Other effective ranges of dosages for metabolites are 0.0024-0.5 mmol/kg 50 and 0.0048-0.25 mmol/kg. Such doses may be administered on a daily, every-other-daily, twice-weekly, weekly, bi-weekly, monthly or other suitable schedule. Essentially the same modes of administration may be employed for the metabolites as for 4-iodo-3 nitrobenzamide-e.g., oral, i.v., ip., etc. Combination Therap 10141] In certain embodiments of the present invention, the methods of the invention further comprise treating uterine cancer, endometrial cancer, or ovarian cancer by administering to a subject a PARP inhibitor with or without at least one anti-tumor agent in combination with another anti-cancer therapy including but not limited to surgery, radiation therapy (e.g., X rays), gene therapy, DNA therapy, adjuvant therapy, neoadjuvant therapy, viral therapy, immunotherapy, RNA therapy, or nanotherapy. [0142] Where the combination therapy further comprises a non-drug treatment, the non drug treatment may be conducted at any suitable time so long as a beneficial effect from the co-action of the combination of the therapeutic agents and non-drug treatment is achieved. For example, in appropriate cases, the beneficial effect is still achieved when the non-drug treatment is temporally removed from the administration of the therapeutic agents, by a significant period of time. The conjugate and the other pharmacologically active agent may be administered to a patient simultaneously, sequentially or in combination. It will be appreciated that when using a combination of the invention, the compound of the invention and the other pharmacologically active agent may be in the same pharmaceutically acceptable carrier and therefore administered simultaneously. They may be in separate pharmaceutical carriers such as conventional oral dosage forms which are taken simultaneously. The term "combination" further refers to the case where the compounds are provided in separate dosage forms and are administered sequentially. Radiation Therapy [0143] Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells. Radiotherapy may be used for curative or adjuvant cancer treatment. It is used as palliative treatment (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where the therapy has survival benefit and it can be curative), Radiotherapy is used for the treatment of malignant tumors and may be used as the primary therapy. It is also common to combine 51 radiotherapy with surgery, chemotherapy, hormone therapy or some mixture of the three. Most common cancer types can be treated with radiotherapy in some way. The precise treatment intent (curative, adjuvant, neoadjuvant, therapeutic, or palliative) will depend on the tumour type, location, and stage, as well as the general health of the patient. 10144] Radiation therapy is commonly applied to the cancerous tumor. The radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with tumor, or if there is thought to be a risk of subclinical malignant spread. It is necessary to include a margin of normal tissue around the tumor to allow for uncertainties in daily set up and internal tumor motion. [01451 Radiation therapy works by damaging the DNA of cells. The damage is caused by a photon, electron, proton, neutron, or ion beam directly or indirectly ionizing the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming free radicals, notably hydroxyl radicals, which then damage the DNA. In the most common forms of radiation therapy, most of the radiation effect is through free radicals. Because cells have mechanisms for repairing DNA damage, breaking the DNA on both strands proves to be the most significant technique in modifying cell characteristics. Because cancer cells generally are undifferentiated and stem cell-like, they reproduce more, and have a diminished ability to repair sub-lethal damage compared to most healthy differentiated cells. The DNA damage is inherited through cell division, accumulating damage to the cancer cells, causing them to die or reproduce more slowly. Proton radiotherapy works by sending protons with varying kinetic energy to precisely stop at the tumor. [0146] Gamma rays are also used to treat some types of cancer including uterine, endometrial, and ovarian cancers. In the procedure called gamma-knife surgery, multiple concentrated beams of gamma rays are directed on the growth in order to kill the cancerous cells. The beams are aimed from different angles to focus the radiation on the growth while minimizing damage to the surrounding tissues. Gene Therapy Agents 101471 Gene therapy agents insert copies of genes into a specific set of a patient's cells, and can target both cancer and non-cancer cells. The goal of gene therapy can be to replace altered genes with functional genes, to stimulate a patient's immune response to cancer, to make cancer cells more sensitive to chemotherapy, to place "suicide" genes into cancer cells, or to inhibit angiogenesis. Genes may be delivered to target cells using viruses, liposomes, or 52 other carriers or vectors. This may be done by injecting the gene-carrier composition into the patient directly, or ex vivo, with infected cells being introduced back into a patient. Such compositions are suitable for use in the present invention. Adjuvant therapy [0148] Adjuvant therapy is a treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, or biological therapy. [0149] Adjuvant chemotherapy is effective for patients with advanced uterine cancer or ovarian cancer. The combination of doxorubicin and cisplatin achieves overall response rates ranging from 34 to 60%, and the addition of paclitaxel seems to improve the outcome of patients with advanced disease, but it induces a significantly higher toxicity. A Gynecologic Oncology Study Group phase-Ill study is currently exploring the triplet paclitaxel+doxorubicin+cisplatin plus G-CSF vs. the less toxic combination of paclitaxel+carboplatin. Ongoing and planned phase-Ill trials are evaluating newer combination chemotherapy regimens, a combination of irradiation and chemotherapy and the implementation of targeted therapies with the goal of improving the tumor control rate and quality of life. 10150] Adjuvant radiation therapy (RT) - Adjuvant radiation therapy significantly reduces the risk that the uterine cancer will recur locally (i.e., in the pelvis or vagina). In general, there are two ways of delivering RT: it may be given as vaginal brachytherapy or as external beam RT (EBRT). In vaginal brachytherapy, brachytherapy delivers RT directly to the vaginal tissues from a source that is temporarily placed inside the body. This allows high doses of radiation to be delivered to the area where cancer cells are most likely to be found. With external beam radiation therapy (EBRT), the source of the radiation is outside the body. 10151] Various therapies including but not limited to hormone therapy, e.g., tamoxifen, or gonadotropin-releasing hormone (GnRH) analogues, and radioactive monoclonal antibody therapy have been used to treat ovarian cancer. Neoadjuvant therapy [0152] Neoadjuvant therapy refers to a treatment given before the primary treatment. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. Neoadjuvant chemotherapy in gynecological cancers is an approach that is shown to 53 have positive effects on survival. It increases the rate of resectability in ovarian and cervical cancers and thus contributes to survival (Ayhan A. et. al. European journal of gynaecological oncology. 2006, vol. 27). Oncolytic viral therapy [0153] Viral therapy for cancer utilizes a type of viruses called oncolytic viruses. An oncolytic virus is a virus that is able to infect and lyse cancer cells, while leaving normal cells unharmed, making them potentially useful in cancer therapy. Replication of oncolytic viruses both facilitates tumor cell destruction and also produces dose amplification at the tumor site. They may also act as vectors for anticancer genes, allowing them to be specifically delivered to the tumor site. 10154] There are two main approaches for generating tumor selectivity: transductional and non-transductional targeting. Transductional targeting involves modifying the specificity of viral coat protein, thus increasing entry into target cells while reducing entry to non-target cells. Non-transductional targeting involves altering the genome of the virus so it can only replicate in cancer cells. This can be done by either transcription targeting, where genes essential for viral replication are placed under the control of a tumor-specific promoter, or by attenuation, which involves introducing deletions into the viral genome that eliminate functions that are dispensable in cancer cells, but not in normal cells. There are also other, slightly more obscure methods. [0155] Chen et al (2001) used CV706, a prostate-specific adenovirus, in conjunction with radiotherapy on prostate cancer in mice, The combined treatment results in a synergistic increase in cell death, as well as a significant increase in viral burst size (the number of virus particles released from each cell lysis). [0156] ONYX-O15 has undergone trials in conjunction with chemotherapy. The combined treatment gives a greater response than either treatment alone, but the results have not been entirely conclusive. ONYX-Ol 5 has shown promise in conjunction with radiotherapy. [0157] Viral agents administered intravenously can be particularly effective against metastatic cancers, which are especially difficult to treat conventionally. However, bloodborne viruses can be deactivated by antibodies and cleared from the blood stream quickly e.g., by Kupffer cells (extremely active phagocytic cells in the liver, which are responsible for adenovirus clearance). Avoidance of the immune system until the tumour is destroyed could be the biggest obstacle to the success of oncolytic virus therapy. To date, no 54 technique used to evade the immune system is entirely satisfactory. It is in conjunction with conventional cancer therapies that oncolytic viruses show the most promise, since combined therapies operate synergistically with no apparent negative effects. [0158] The specificity and flexibility of oncolytic viruses means they have the potential to treat a wide range of cancers including uterine cancer, endometrial cancer, and ovarian cancer with minimal side effects. Oncolytic viruses have the potential to solve the problem of selectively killing cancer cells. Nanotherapy [0159] Nanometer-sized particles have novel optical, electronic, and structural properties that are not available from either individual molecules or bulk solids. When linked with tumor-targeting moieties, such as tumor-specific ligands or monoclonal antibodies, these nanoparticles can be used to target cancer-specific receptors, tumor antigens (biomarkers), and tumor vasculatures with high affinity and precision. The formulation and manufacturing process for cancer nanotherapy is disclosed in patent US7179484, and article M. N. Kbalid, P. Simard, D. I-oarau, A. Dragomir, J. Leroux, Long Circulating Poly(Ethylene Glycol)Decorated Lipid Nanocapsules Deliver Docetaxel to Solid Tumors, Pharmaceutical Research, 23(4), 2006, all of which are herein incorporated by reference in their entireties. RNA therapy 10160] RNA including but not limited to siRNA, shRNA, microRNA may be used to modulate gene expression and treat cancers. Double stranded oligonucleotides are formed by the assembly of two distinct oligonucleotide sequences where the oligonucleotide sequence of one strand is complementary to the oligonucleotide sequence of the second strand; such double stranded oligonucleotides are generally assembled from two separate oligonucleotides (e.g., siRNA), or from a single molecule that folds on itself to form a double stranded structure (e.g., shRNA or short hairpin RNA). These double stranded oligonucleotides known in the art all have a common feature in that each strand of the duplex has a distinct nucleotide sequence, wherein only one nucleotide sequence region (guide sequence or the antisense sequence) has complementarity to a target nucleic acid sequence and the other strand (sense sequence) comprises nucleotide sequence that is homologous to the target nucleic acid sequence. 55 [0161] MicroRNAs (miRNA) are single-stranded RNA molecules of about 21-23 nucleotides in length, which regulate gene expression. miRNAs are encoded by genes that are transcribed from DNA but not translated into protein (non-coding RNA); instead they are processed from primary transcripts known as pri-miRNA to short stem-loop structures called pre-miRNA and finally to functional miRNA. Mature miRNA molecules are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to downregulate gene expression. [0162] Certain RNA inhibiting agents may be utilized to inhibit the expression or translation of messenger RNA ("mRNA") that is associated with a cancer phenotype. Examples of such agents suitable for use herein include, but are not limited to, short interfering RNA ("siRNA"), ribozymes, and antisense oligonucleotides. Specific examples of RNA inhibiting agents suitable for use herein include, but are not limited to, Cand5, Sirna 027, fomivirsen, and angiozyme. Small Molecule Enzymatic Inhibitors 10163] Certain small molecule therapeutic agents are able to target the tyrosine kinase enzymatic activity or downstream signal transduction signals of certain cell receptors such as epidermal growth factor receptor ("EGFR") or vascular endothelial growth factor receptor ("VEGFR"). Such targeting by small molecule therapeutics can result in anti-cancer effects. Examples of such agents suitable for use herein include, but are not limited to, imatinib, gefitinib, erlotinib, lapatinib, canertinib, ZD6474, sorafenib (BAY 43-9006), ERB-569, and their analogues and derivatives. Anti-Metastatic Agents 10164] The process whereby cancer cells spread from the site of the original tumor to other locations around the body is termed cancer metastasis. Certain agents have anti-metastatic properties, designed to inhibit the spread of cancer cells. Examples of such agents suitable for use herein include, but are not limited to, marimastat, bevacizumab, trastuzumab, rituximab, erlotinib, MMI- 166, GRN 1 63L, hunter-killer peptides, tissue inhibitors of metalloproteinases (TIMPs), their analogues, derivatives and variants. Chemopreventative agents 56 10165] Certain pharmaceutical agents can be used to prevent initial occurrences of cancer, or to prevent recurrence or metastasis. Administration with such chemopreventative agents in combination with eflornithine-NSAID conjugates of the invention can act to both treat and prevent the recurrence of cancer. Examples of chemopreventative agents suitable for use herein include, but are not limited to, tamoxifen, raloxifene, tibolone, bisphosphonate, ibandronate, estrogen receptor modulators, aromatase inhibitors (letrozole, anastrozole), luteinizing hormone-releasing hormone agonists, goserelin, vitamin A, retinal, retinoic acid, fenretinide, 9-cis-retinoid acid, 13-cis-retinoid acid, all-trans-retinoic acid, isotretinoin, tretinoid, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, cyclooxygenase inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, ibuprofen, celecoxib, polyphenols, polyphenol E, green tea extract, folic acid, glucaric acid, interferon-alpha, anethole dithiolethione, zinc, pyridoxine, finasteride, doxazosin, selenium, indole-3-carbinal, alpha-difluoromethylornithine, carotenoids, beta-carotene, lycopene, antioxidants, coenzyme Q10, flavonoids, quercetin, curcumin, catechins, epigallocatechin gallate, N-acetylcysteine, indole-3-carbinol, inositol hexaphosphate, isoflavones, glucanic acid, rosemary, soy, saw palmetto, and calcium. An additional example of chemopreventative agents suitable for use in the present invention is cancer vaccines. These can be created through immunizing a patient with all or part of a cancer cell type that is targeted by the vaccination process. Clinical Efficacy 101661 Clinical efficacy may be measured by any method known in the art. In some embodiments, clinical efficacy of the therapeutic treatments described herein may be determined by measuring the clinical benefit rate (CBR). The clinical benefit rate is measured by determining the sum of the percentage of patients who are in complete remission (CR), the number of patients who are in partial remission (PR) and the number of patients having stable disease (SD) at a time point at least 6 months out from the end of therapy. The shorthand for this formula is CBR = CR +I PR -- SD ;> 6 months. The CBR for combination therapy with paclitaxel and carboplatin is 45%. Thus, the CBR for triple combination therapy with a taxane, platinum complex and PARP inhibitor (e.g., paclitaxel, carboplatin and 4-iodo-3-nitrobenzamide; CBR(cac) may be compared to that of the double combination therapy with paclitaxel and carboplatin (CBRoc). Similarly, the CBR for combination therapy with an antimetabolite (e.g., gemeitabine), a platinum compound (e.g., carboplatin), and a PA RP inhibitor (e.g., 4-iodo-3-nitrobenzamide) (CBRo-mI/c'AiIBoMA) may 57 be compared to that of the double combination therapy with an antimetabolite (e.g., gemcitabine) and a platinum compound (e.g., carboplatin) (CBRGEM/CARBO). In some embodiments, CBRGEM/CARBO/BA is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or more. In some embodiments, the CBR is at least about 30%, at least about 40%, or at least about 50%. [0167] In some embodiments disclosed herein, the methods include pre-determining that a cancer is treatable by PARP inhibitors. Some such methods comprise identifying a level of PARP in a uterine, endometrial, or ovarian cancer sample of a patient, determining whether the level of PARP expression in the sample is greater than a pre-determined value, and, if the PARP expression is greater than said predetermined value, treating the patient with a combination of an anti-tumor agent described herein and a PARP inhibitor such as 4-iodo-3 nitrobenzamide. In other embodiments, the methods comprise identifying a level of PARP in a uterine, endometrial, or ovarian cancer sample of a patient, determining whether the level of PARP expression in the sample is greater than a pre-determined value, and, if the PARP expression is greater than said predetermined value, treating the patient with a PARP inhibitor, such as 4-iodo-3 -nitrobenzamide. 101681 Uterine tumors in women who inherit faults in either the BRCA1 or BRCA2 genes occur because the tumor cells have lost a specific mechanism that repair damaged DNA. BRCA 1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to uterine and other cancers. PARP is involved in base excision repair, a pathway in the repair of DNA single-strand breaks. BRCAl or BRCA2 dysfunction sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis (Jones C, Plummer ER. PARP inhibitors and cancer therapy - early results and potential applications. Br J Radiol. 2008 Oct;81 Spec No 1:S2-5; Drew Y, Calvert HI. The potential of PARP inhibitors in genetic breast and ovarian cancers. Ann N Y Acad Sci. 2008 Sep;l 138:136-45; Farmer H, et al., Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917-21). [0169] Patients deficient in BRCA genes may have up-regulated levels of PARP. PARP up-regulation may be an indicator of other defective DNA-repair pathways and unrecognized BRCA-like genetic defects. Assessment of PARP gene expression and impaired DNA repair especially defective homologous recombination DNA repair can be used as an indicator of tumor sensitivity to PARP inhibitor. Hence, in some embodiments, treatment of uterine cancer can be enhanced not only by determining the HR and/or IER2 status of the cancer, 58 but also by identifying early onset of cancer in BRCA and homologous recombination DNA repair deficient patients by measuring the level of PARP. The BRCA and homologous recombination DNA repair deficient patients treatable by PARP inhibitors can be identified if PARP is up-regulated. Further, such homologous recombination DNA repair deficient patients can be treated with PARP inhibitors. [0170] In some embodiments, a sample is collected from a patient having a uterine lesion suspected of being cancerous. While such sample may be any available biological tissue, in most cases the sample will be a portion of the suspected uterine lesion, whether obtained by laparoscopy or open surgery (e.g., a hysterectomy). PARP expression may then be analyzed and, if the PARP expression is above a predetermined level (e.g., is up-regulated compared to normal tissue) the patient may be treated with a PARP inhibitor in combination with an antimetabolite (e.g., gemcitabine), a platinum compound (e.g., carboplatin), and a PARP inhibitor (e.g., 4-iodo-3-nitrobenzamide). It is thus to be understood that, while embodiments described herein are directed to treatment of endometrial cancer, recurrent, advanced, or persistent uterine cancer, and ovarian cancer in association with a BRCA-defect, in some embodiments, the uterine or ovarian cancer need not have these characteristics so long as the threshold PARP up-regulation is satisfied. 101711 In some embodiments, tumors that are homologous recombination deficient are identified by evaluating levels of PARP expression. If up-regulation of PARP is observed, such tumors can be treated with PARP inhibitors. Another embodiment is a method for treating a homologous recombination deficient cancer comprising evaluating level of PARP expression and, if overexpression is observed, the cancer is treated with a PARP inhibitor. Sample collection, preparation and separation [01721 Biological samples may be collected from a variety of sources from a patient including a body fluid sample, or a tissue sample. Samples collected can be human normal and tumor samples, nipple aspirants. The samples can be collected from individuals repeatedly over a longitudinal period of time (e.g., about once a day, once a week, once a month, biannually or annually). Obtaining numerous samples from an individual over a period of time can be used to verify results from earlier detections and/or to identify an alteration in biological pattern as a result of, for example, disease progression, drug treatment, etc. 59 10173] Sample preparation and separation can involve any of the procedures, depending on the type of sample collected and/or analysis of PARP. Such procedures include, by way of example only, concentration, dilution, adjustment of pH, removal of high abundance polypeptides (e.g., albumin, gamma globulin, and transferin, etc.), addition of preservatives and calibrants, addition of protease inhibitors, addition of denaturants, desalting of samples, concentration of sample proteins, extraction and purification of lipids. [0174] The sample preparation can also isolate molecules that are bound in non-covalent complexes to other protein (e.g., carrier proteins). This process may isolate those molecules bound to a specific carrier protein (e.g., albumin), or use a more general process, such as the release of bound molecules from all carrier proteins via protein denaturation, for example using an acid, followed by removal of the carrier proteins. 101751 Removal of undesired proteins (e.g., high abundance, uninformative, or undetectable proteins) from a sample can be achieved using high affinity reagents, high molecular weight filters, ultracentrifugation and/or electrodialysis. High affinity reagents include antibodies or other reagents (e.g., aptamers) that selectively bind to high abundance proteins. Sample preparation could also include ion exchange chromatography, metal ion affinity chromatography, gel filtration, hydrophobic chromatography, chromatofocusing, adsorption chromatography, isoelectric focusing and related techniques. Molecular weight filters include membranes that separate molecules on the basis of size and molecular weight. Such filters may further employ reverse osmosis, nanofiltration, ultrafiltration and micro filtration. 10176] Ultracentrifugation is a method for removing undesired polypeptides from a sample. Ultracentrifugation is the centrifugation of a sample at about 15,000-60,000 rpm while monitoring with an optical system the sedimentation (or lack thereof) of particles. Electrodialysis is a procedure which uses an electromembrane or semipermable membrane in a process in which ions are transported through semi-permeable membranes from one solution to another under the influence of a potential gradient. Since the membranes used in electrodialysis may have the ability to selectively transport ions having positive or negative charge, reject ions of the opposite charge, or to allow species to migrate through a semipermable membrane based on size and charge, it renders electrodialysis useful for concentration, removal, or separation of electrolytes. [0177] Separation and purification in the present invention may include any procedure known in the art, such as capillary electrophoresis (e.g., in capillary or on-chip) or chromatography (e.g., in capillary, column or on a chip). Electrophoresis is a method which 60 can be used to separate ionic molecules under the influence of an electric field. Electrophoresis can be conducted in a gel, capillary, or in a microchannel on a chip. Examples of gels used for electrophoresis include starch, acrylamide, polyethylene oxides, agarose, or combinations thereof. A gel can be modified by its cross-linking, addition of detergents, or denaturants, immobilization of enzymes or antibodies (affinity electrophoresis) or substrates (zymography) and incorporation of a pH gradient. Examples of capillaries used for electrophoresis include capillaries that interface with an electrospray. [0178] Capillary electrophoresis (CE) is preferred for separating complex hydrophilic molecules and highly charged solutes. CE technology can also be implemented on microfluidic chips. Depending on the types of capillary and buffers used, CE can be further segmented into separation techniques such as capillary zone electrophoresis (CZE), capillary isoelectric focusing chief) , capillary isotachophoresis (cITP) and capillary electrochromatography (CEC). An embodiment to couple CE techniques to electrospray ionization involves the use of volatile solutions, for example, aqueous mixtures containing a volatile acid and/or base and an organic such as an alcohol or acetonitrile. {0179] Capillary isotachophoresis (cITP) is a technique in which the analytes move through the capillary at a constant speed but are nevertheless separated by their respective mobilities. Capillary zone electrophoresis (CZE), also known as free-solution CE (FSCE), is based on differences in the electrophoretic mobility of the species, determined by the charge on the molecule, and the frictional resistance the molecule encounters during migration which is often directly proportional to the size of the molecule. Capillary isoelectric focusing (CIEF) allows weakly-ionizable amphoteric molecules, to be separated by electrophoresis in a pH gradient. CEC is a hybrid technique between traditional high performance liquid chromatography (HPLC) and CE. 101801 Separation and purification techniques used in the present invention include any chromatography procedures known in the art. Chromatography can be based on the differential adsorption and elution of certain analytes or partitioning of analytes between mobile and stationary phases. Different examples of chromatography include, but not limited to, liquid chromatography (LC), gas chromatography (GC), high performance liquid chromatography (HPLC) etc. Measuring levels of PARP expression 61 [0181] The poly (ADP-ribose) polymerase (PARP) is also known as poly (ADP-ribose) synthase and poly ADP-ribosyltransferase. PARP catalyzes the formation of poly (ADP ribose) polymers which can attach to cellular proteins (as well as to itself) and thereby modify the activities of those proteins. The enzyme plays a role in enhancing DNA repair, but it also plays a role in regulation of transcription, cell proliferation, and chromatin remodeling (for review see: D. D'amours et al., "Poly (ADP-ribosylation reactions in the regulation of nuclear functions," Biochem. J. 342: 249-268 (1999)). [0182] PARP-1 comprises an N-terminal DNA binding domain, an automodification domain and a C-terminal catalytic domain and various cellular proteins interact with PARP- 1 The N-terminal DNA binding domain contains two zinc finger motifs. Transcription enhancer factor-I (TEF-1), retinoid X receptor a, DNA polymerase a, X-ray repair cross complementing factor-1 (XRCC1) and PARP-1 itself interact with PARP-l in this domain. The automodification domain contains a BRCT motif, one of the protein-protein interaction modules. This motif is originally found in the C-terminus of BRCAl (uterine cancer susceptibility protein 1) and is present in various proteins related to DNA repair, recombination and cell-cycle checkpoint control. POU-homeodomain-containing octamer transcription factor-i (Oct-1), Yin Yang (YY)1 and ubiquitin-conjugating enzyme 9 (ubc9) could interact with this BRCT motif in PARP-1. 101831 More than 15 members of the PARP family of genes are present in the maninmmalian genome. PARP family proteins and poly(ADP-ribose) glycohydrolase (PARG), which degrades poly(ADP-ribose) to ADP-ribose, could be involved in a variety of cell regulatory functions including DNA damage response and transcriptional regulation and may be related to carcinogenesis and the biology of cancer in many respects. [0184] Several PARP family proteins have been identified. Tankyrase has been found as an interacting protein of telomere regulatory factor I (TRF-i) and is involved in telomere regulation. Vault PARP (VPARP) is a component in the vault complex, which acts as a nuclear-cytoplasmic transporter. PARP-2, PARP-3 and 2,3,7,8-tetrachlorodibenzo-p-dioxin inducible PARP (TiPARP) have also been identified. Therefore, poly (ADP-ribose) metabolism could be related to a variety of cell regulatory functions. [0185] A member of this gene family is PARP-1. The PARP-I gene product is expressed at high levels in the nuclei of cells and is dependent upon DNA damage for activation. Without being bound by any theory, it is believed that PARP-I binds to DNA single or double stranded breaks through an amino terminal DNA binding domain. The binding activates the carboxy terminal catalytic domain and results in the formation of polymers of 62 ADP-ribose on target molecules. PARP-1 is itself a target of poly ADP-ribosylation by virtue of a centrally located automodification domain. The ribosylation of PARP-1 causes dissociation of the PARP-1 molecules from the DNA. The entire process of binding, ribosylation, and dissociation occurs very rapidly. It has been suggested that this transient binding of PARP-1 to sites of DNA damage results in the recruitment of DNA repair machinery or may act to suppress the recombination long enough for the recruitment of repair machinery. [0186] The source of ADP-ribose for the PARP reaction is nicotinamide adenosine dinucleotide (NAD). NAD is synthesized in cells from cellular ATP stores and thus high levels of activation of PARP activity can rapidly lead to depletion of cellular energy stores. It has been demonstrated that induction of PARP activity can lead to cell death that is correlated with depletion of cellular NAD and ATP pools. PARP activity is induced in many instances of oxidative stress or during inflammation. For example, during reperfusion of ischemic tissues reactive nitric oxide is generated and nitric oxide results in the generation of additional reactive oxygen species including hydrogen peroxide, peroxynitrate and hydroxyl radical. These latter species can directly damage DNA and the resulting damage induces activation of PARP activity. Frequently, it appears that sufficient activation of PARP activity occurs such that the cellular energy stores are depleted and the cell dies. A similar mechanism is believed to operate during inflammation when endothelial cells and pro inflammatory cells synthesize nitric oxide which results in oxidative DNA damage in surrounding cells and the subsequent activation of PARP activity. The cell death that results from PARP activation is believed to be a major contributing factor in the extent of tissue damage that results from ischemia-reperfusion injury or from inflammation. [01871 In some embodiments, the level of PARP in a sample from a patient is compared to predetermined standard sample. The sample from the patient is typically from a diseased tissue, such as cancer cells or tissues. The standard sample can be from the same patient or from a different subject. The standard sample is typically a normal, non-diseased sample. However, in some embodiments, such as for staging of disease or for evaluating the efficacy of treatment, the standard sample is from a diseased tissue. The standard sample can be a combination of samples from several different subjects. In some embodiments, the level of PARP from a patient is compared to a pre-determined level. This pre-determined level is typically obtained from normal samples, As described herein, a "pre-determined PARP level" may be a level of PARP used to, by way of example only, evaluate a patient that may be selected lor treatment, evaluate a response to a PARP inhibitor treatment, evaluate a 63 response to a combination of a PARP inhibitor and a second therapeutic agent treatment, and/or diagnose a patient for cancer, inflammation, pain and/or related conditions. A pre determined PARP level may be determined in populations of patients with or without cancer. The pre-determined PARP level can be a single number, equally applicable to every patient, or the pre-determined PARP level can vary according to specific subpopulations of patients. For example, men might have a different pre-determined PARP level than women; non smokers may have a different pre-determined PARP level than smokers. Age, weight, and height of a patient may affect the pre-determined PARP level of the individual. Furthermore, the pre-determined PARP level can be a level determined for each patient individually. The pre-determined PARP level can be any suitable standard. For example, the pre-determined PARP level can be obtained from the same or a different human for whom a patient selection is being assessed. In one embodiment, the pre-determined PARP level can be obtained from a previous assessment of the same patient. In such a manner, the progress of the selection of the patient can be monitored over time. In addition, the standard can be obtained from an assessment of another human or multiple humans, e.g., selected groups of humans. In such a manner, the extent of the selection of the human for whom selection is being assessed can be compared to suitable other humans, e.g., other humans who are in a similar situation to the human of interest, such as those suffering from similar or the same condition(s). [0188] In some embodiments of the present invention the change of PARP from the pre determined level is about 0.5 fold, about 1.0 fold, about 1.5 fold, about 2.0 fold, about 2.5 fold, about 3.0 fold, about 3.5 fold, about 4.0 fold, about 4.5 fold, or about 5.0 fold. In some embodiments is fold change is less than about 1, less than about 5, less than about 10, less than about 20, less than about 30, less than about 40, or less than about 50. In other embodiments, the changes in PARP level compared to a predetermined level is more than about 1, more than about 5, more than about 10, more than about 20, more than about 30, more than about 40, or more than about 50. Preferred fold changes from a pre-determined level are about 0.5, about 1.0, about 1.5, about 2.0, about 2.5, and about 3.0, [0189] The analysis of PARP levels in patients is particularly valuable and informative, as it allows the physician to more effectively select the best treatments, as well as to utilize more aggressive treatments and therapy regimens based on the up-regulated or down-regulated level of PARP. More aggressive treatment, or combination treatments and regimens, can serve to counteract poor patient prognosis and overall survival time. Armed with this information, the medical practitioner can choose to provide certain types of treatment such as treatment with PARP inhibitors, and/or more aggressive therapy. 64 10190] In monitoring a patient's PARP levels, over a period of time, which may be days, weeks, months, and in some cases, years, or various intervals thereof, the patient's body fluid sample, e.g., serum or plasma, can be collected at intervals, as determined by the practitioner, such as a physician or clinician, to determine the levels of PARP, and compared to the levels in normal individuals over the course or treatment or disease. For example, patient samples can be taken and monitored every month, every two months, or combinations of one, two, or three month intervals according to the invention. In addition, the PARP levels of the patient obtained over time can be conveniently compared with each other, as well as with the PARP values, of normal controls, during the monitoring period, thereby providing the patient's own PARP values, as an internal, or personal, control for long-term PARP monitoring. Techniques for Analysis of PARP [0191] Previous studies have shown increased PARP activity in ovarian cancers, hepatocellular carcinomas, and rectal tumors, compared with normal healthy control tissues, as well as in human peripheral blood lymphocytes from leukemia patients (Yalcintepe L, et al., J Med Biol Res 2005;38:361-5. Singh N. et al., Cancer Lett 1991;58:131-5; Nomura F, et al., J (astroenterol Hepatol 2000;15:529-35). Thus, assessing PARP activity in a tumor cell would allow one of ordinary skill in the art to determine whether a particular tumor would benefit from treatment with a PARP inhibitor such as 4-iodo-3-nitrobenzamide. See, e.g., U.S. Patent Publication No. US 2009/0123419 Al, which is incorporated herein by reference. [0192] The analysis of the PARP may include analysis of PARP gene expression, including an analysis of DNA, RNA, analysis of the level of PARP and/or analysis of the activity of PARP including a level of mono- and poly-ADP-ribozylation. Without limiting the scope of the present invention, any number of techniques known in the art can be employed for the analysis of PARP and they are all within the scope of the present invention. Some of the examples of such detection technique are given below but these examples are in no way limiting to the various detection techniques that can be used in the present invention. [0193] Gene Expression Profiling: Methods of gene expression profiling include methods based on hybridization analysis of polynucleotides, polyribonucleotides methods based on sequencing of polynucleotides, polyribonucleotides and proteomics-based methods. The most commonly used methods known in the art for the quantification of mRNA expression in a sample include northern blotting and in situ hybridization (Parker & Barnes, Methods in Molecular Biology 106:247-283 (1999)); RNAse protection assays (Hod, Biotechniques 65 13:852-854 (1992)); and PCR-based methods, such as reverse transcription polymerase chain reaction (RT-PCR) (Weis et al., Trends in Genetics 8:263-264 (1992)). Alternatively, antibodies may be employed that can recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS), Comparative Genome Hybridisation (CGH), Chromatin Immunoprecipitation (ChIP), Single nucleotide polymorphism (SNP) and SNP arrays, Fluorescent in situ Hybridization (FISH), Protein binding arrays and DNA microarray (also commonly known as gene or genome chip, DNA chip, or gene array), RNAmicroarrays. [0194] Reverse Transcriptase PCR (RT-PCR): One of the most sensitive and most flexible quantitative PCR-based gene expression profiling methods is RT-PCR, which can be used to compare mRNA levels in different sample populations, in normal and tumor tissues, with or without drug treatment, to characterize patterns of gene expression, to discriminate between closely related mRNAs, and to analyze RNA structure. [0195] The first step is the isolation of mRNA from a target sample. For example, the starting material can be typically total RNA isolated from human tumors or tumor cell lines, and corresponding normal tissues or cell lines, respectively. Thus RNA can be isolated from a variety of normal and diseased cells and tissues, for example tumors, including breast, lung, colorectal, prostate, brain, liver, kidney, pancreas, spleen, thymus, testis, ovary, uterus, etc., or tumor cell lines,. If the source of mRNA is a primary tumor, mRNA can be extracted, for example, from frozen or archived fixed tissues, for example paraffin-embedded and fixed (e.g., formalin-fixed) tissue samples. General methods for mRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al., Current Protocols of Molecular Biology, John Wiley and Sons (1997). 101961 In particular, RNA isolation can be performed using purification kit, buffer set and protease from commercial manufacturers, according to the manufacturer's instructions. RNA prepared from tumor can be isolated, for example, by cesium chloride density gradient centrifugation. As RNA cannot serve as a template for PCR, the first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by its exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MMLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on 66 the circumstances and the goal of expression profiling. The derived cDNA can then be used as a template in the subsequent PCR reaction. [0197] To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard is expressed at a constant level among different tissues, and is unaffected by the experimental treatment. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and I-actin. [01981 A more recent variation of the RT-PCR technique is the real tine quantitative PCR, which measures PCR product accumulation through a dual-labeled fluorigenic probe. Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT PCR. [0199j Fluorescence Microscopy: Some embodiments of the invention include fluorescence microscopy for analysis of PARP. Fluorescence microscopy enables the molecular composition of the structures being observed to be identified through the use of fluorescently-labeled probes of high chemical specificity such as antibodies. It can be done by directly conjugating a fluorophore to a protein and introducing this back into a cell. Fluorescent analogue may behave like the native protein and can therefore serve to reveal the distribution and behavior of this protein in the cell. Along with NMR, infrared spectroscopy, circular dichroism and other techniques, protein intrinsic fluorescence decay and its associated observation of fluorescence anisotropy, collisional quenching and resonance energy transfer are techniques for protein detection. The naturally fluorescent proteins can be used as fluorescent probes. The jellyfish aequorea victoria produces a naturally fluorescent protein known as green fluorescent protein (GFP). The fusion of these fluorescent probes to a target protein enables visualization by fluorescence microscopy and quantification by flow cytometry. [02001 By way of example only, some of the probes are labels such as, fluorescein and its derivatives, carboxyfluoresceins, rhodamines and their derivatives, atto labels, fluorescent red and fluorescent orange: cy3/cy5 alternatives, lanthanide complexes with long lifetimes, long wavelength labels - up to 800 nm, DY cyanine labels, and phycobili proteins. By way of example only, some of the probes are conjugates such as, isothiocyanate conjugates, streptavidin conjugates, and biotin conjugates. By way of example only, some of the probes are enzyme substrates such as, fluorogenic and chromogenic substrates. By way of example 67 only, some of the probes are fluorochromes such as, FITC (green fluorescence, excitation/emission = 506/529 nm), rhodamine B (orange fluorescence, excitation/emission = 560/584 nm), and nile blue A (red fluorescence, excitation/emission = 636/686 nm). Fluorescent nanoparticles can be used for various types of immunoassays. Fluorescent nanoparticles are based on different materials, such as, polyacrylonitrile, and polystyrene etc. Fluorescent molecular rotors are sensors of microenvironmental restriction that become fluorescent when their rotation is constrained. Few examples of molecular constraint include increased dye (aggregation), binding to antibodies, or being trapped in the polymerization of actin. IEF (isoelectric focusing) is an analytical tool for the separation of ampholytes, mainly proteins. An advantage for IEF-gel electrophoresis with fluorescent IEF-marker is the possibility to directly observe the formation of gradient. Fluorescent IEF-marker can also be detected by UV-absorption at 280 nm (20 0 C). [02011 A peptide library can be synthesized on solid supports and, by using coloring receptors, subsequent dyed solid supports can be selected one by one. If receptors cannot indicate any color, their binding antibodies can be dyed. The method can not only be used on protein receptors, but also on screening binding ligands of synthesized artificial receptors and screening new metal binding ligands as well. Automated methods for HTS and FACS (fluorescence activated cell sorter) can also be used, A FACS machine originally runs cells through a capillary tube and separates cells by detecting their fluorescent intensities. 102021 Immunoassays: Some embodiments of the invention include immunoassay for the analysis of PARP. In immunoblotting like the western blot of electrophoretically separated proteins a single protein can be identified by its antibody. Immunoassay can be competitive binding immunoassay where analyte competes with a labeled antigen for a limited pool of antibody molecules (e.g., radioimmunoassay, EMIT). Immunoassay can be non-competitive where antibody is present in excess and is labeled. As analyte antigen complex is increased, the amount of labeled antibody-antigen complex may also increase (e.g., ELISA). Antibodies can be polyclonal if produced by antigen injection into an experimental animal, or monoclonal if produced by cell fusion and cell culture techniques. In imnunoassay, the antibody may serve as a specific reagent for the analyte antigen. 10203] Without limiting the scope and content of the present invention, some of the types of immunoassays are, by way of example only, RIAs (radioimmunoassay), enzyme immunoassays like ELISA (enzyme-I Inked immunosorbent assay), EMIT (enzyme multiplied immunoassay technique), microparticle enzyme immunoassay (MEIA), LIA (luminescent immunoassay), and FIA (fluorescent immunoassay). These techniques can be used to detect 68 biological substances in the nasal specimen. The antibodies - either used as primary or secondary ones - can be labeled with radioisotopes (e.g., 1251), fluorescent dyes (e.g., FITC) or enzymes (e.g., HRP or AP) which may catalyse fluorogenic or luminogenic reactions. [0204] Biotin, or vitamin H is a co-enzyme which inherits a specific affinity towards avidin and streptavidin. This interaction makes biotinylated peptides a useful tool in various biotechnology assays for quality and quantity testing. To improve biotin/streptavidin recognition by minimizing steric hindrances, it can be necessary to enlarge the distance between biotin and the peptide itself This can be achieved by coupling a spacer molecule (e.g., 6-nitrohexanoic acid) between biotin and the peptide. [0205] The biotin quantitation assay for biotinylated proteins provides a sensitive fluorometric assay for accurately determining the number of biotin labels on a protein. Biotinylated peptides are widely used in a variety of biomedical screening systems requiring immobilization of at least one of the interaction partners onto streptavidin coated beads, membranes, glass slides or microtiter plates. The assay is based on the displacement of a ligand tagged with a quencher dye from the biotin binding sites of a reagent. To expose any biotin groups in a multiply labeled protein that are sterically restricted and inaccessible to the reagent, the protein can be treated with protease for digesting the protein. 102061 EMIT is a competitive binding immunoassay that avoids the usual separation step. A type of immunoassay in which the protein is labeled with an enzyme, and the enzyme protein-antibody complex is enzymatically inactive, allowing quantitation of unlabelled protein. Some embodiments of the invention include ELISA to analyze PARP. ELISA is based on selective antibodies attached to solid supports combined with enzyme reactions to produce systems capable of detecting low levels of proteins. It is also known as enzyme immunoassay or EIA. The protein is detected by antibodies that have been made against it, that is, for which it is the antigen. Monoclonal antibodies are often used. [02071 The test may require the antibodies to be fixed to a solid surface, such as the inner surface of a test tube, and a preparation of the same antibodies coupled to an enzyme. The enzyme may be one (e.g., P-galactosidase) that produces a colored product from a colorless substrate. The test, for example, may be performed by filling the tube with the antigen solution (e.g., protein) to be assayed. Any antigen molecule present may bind to the immobilized antibody molecules. The antibody-enzyme conjugate may be added to the reaction mixture. The antibody part of the conjugate binds to any antigen molecules that are bound previously, creating an antibody-antigen-anti body "sandwich". After washing away any unbound conjugate, the substrate solution may be added. After a set interval, the reaction 69 is stopped (e.g., by adding I N NaOH) and the concentration of colored product formed is measured in a spectrophotometer. The intensity of color is proportional to the concentration of bound antigen. [0208] ELISA can also be adapted to measure the concentration of antibodies, in which case, the wells are coated with the appropriate antigen. The solution (e.g., serum) containing antibody may be added. After it has had time to bind to the immobilized antigen, an enzyme conjugated anti-immunoglobulin may be added, consisting of an antibody against the antibodies being tested for. After washing away unreacted reagent, the substrate may be added. The intensity of the color produced is proportional to the amount of enzyme-labeled antibodies bound (and thus to the concentration of the antibodies being assayed). [0209] Some embodiments of the invention include radioimmunoassays to analyze PARP. Radioactive isotopes can be used to study in vivo metabolism, distribution, and binding of small amount of compounds. Radioactive isotopes of H, 12 C, 31 P, 3S, and 127 in body are used such as 3 H, 14c, 32 p, 35S, and 1251. In receptor fixation method in 96 well plates, receptors may be fixed in each well by using antibody or chemical methods and radioactive labeled ligands may be added to each well to induce binding. Unbound ligands may be washed out and then the standard can be determined by quantitative analysis of radioactivity of bound ligands or that of washed-out ligands. Then, addition of screening target compounds may induce competitive binding reaction with receptors. If the compounds show higher affinity to receptors than standard radioactive ligands, most of radioactive ligands would not bind to receptors and may be left in solution. Therefore, by analyzing quantity of bound radioactive ligands (or washed-out ligands), testing compounds' affinity to receptors can be indicated. 102101 The filter membrane method may be needed when receptors cannot be fixed to 96 well plates or when ligand binding needs to be done in solution phase. In other words, after ligand-receptor binding reaction in solution, if the reaction solution is filtered through nitrocellulose filter paper, small molecules including ligands may go through it and only protein receptors may be left on the paper. Only ligands that strongly bound to receptors may stay on the filter paper and the relative affinity of added compounds can be identified by quantitative analysis of the standard radioactive ligands. [0211] Some embodiments of the invention include fluorescence immunoassays for the analysis of PARP. Fluorescence based immunological methods are based upon the competitive binding of labeled ligands versus unlabeled ones on highly specific receptor sites. The fluorescence technique can be used for immunoassays based on changes in 70 fluorescence lifetime with changing analyte concentration. This technique may work with short lifetime dyes like fluorescein isothiocyanate (FITC) (the donor) whose fluorescence may be quenched by energy transfer to eosin (the acceptor). A number of photolumineseent compounds may be used, such as cyanines, oxazines, thiazines, porphyrins, phthalocyanines, fluorescent infrared-emitting polynuclear aromatic hydrocarbons, phycobiliproteins, squaraines and organo-metallic complexes, hydrocarbons and azo dyes. [0212] Fluorescence based immunological methods can be, for example, heterogenous or homogenous. Heterogenous immunoassays comprise physical separation of bound from free labeled analyte. The analyte or antibody may be attached to a solid surface. The technique can be competitive (for a higher selectivity) or noncompetitive (for a higher sensitivity). Detection can be direct (only one type of antibody used) or indirect (a second type of antibody is used). Homogenous immunoassays comprise no physical separation. Double antibody fluorophore-labeled antigen participates in an equilibrium reaction with antibodies directed against both the antigen and the fluorophore. Labeled and unlabeled antigen may compete for a limited number of anti-antigen antibodies. [0213] Some of the fluorescence immunoassay methods include simple fluorescence labeling method, fluorescence resonance energy transfer (FRET), time resolved fluorescence (TRF), and scanning probe microscopy (SPM). The simple fluorescence labeling method can be used for receptor-ligand binding, enzymatic activity by using pertinent fluorescence, and as a fluorescent indicator of various in vivo physiological changes such as p1, ion concentration, and electric pressure. TRF is a method that selectively measures fluorescence of the lanthanide series after the emission of other fluorescent molecules is finished. TRF can be used with FRET and the lanthanide series can become donors or acceptors. In scanning probe microscopy, in the capture phase, for example, at least one monoclonal antibody is adhered to a solid phase and a scanning probe microscope is utilized to detect antigen/antibody complexes which may be present on the surface of the solid phase. The use of scanning tunneling microscopy eliminates the need for labels which normally is utilized in many immunoassay systems to detect antigen/antibody complexes. 10214] Protein identification methods: By way of example only, protein identification methods include low-throughput sequencing through Edman degradation, mass spectrometry techniques, peptide mass fingerprinting, de novo sequencing, and antibody-based assays. The protein quantification assays include fluorescent dye gel staining, tagging or chemical modification methods (i.e. isotope-coded affinity tags (ICATS), combined fractional diagonal chromatography (COFRADIC)). The purified protein may also be used for determination of 71 three-dimensional crystal structure, which can be used for modeling intermolecular interactions. Common methods for determining three-dimensional crystal structure include x-ray crystallography and NMR spectroscopy. Characteristics indicative of the three dimensional structure of proteins can be probed with mass spectrometry. By using chemical crosslinking to couple parts of the protein that are close in space, but far apart in sequence, information about the overall structure can be inferred. By following the exchange of amide protons with deuterium from the solvent, it is possible to probe the solvent accessibility of various parts of the protein. [0215] In one embodiment, fluorescence-activated cell-sorting (FACS) is used to identify PARP expressing cells. FACS is a specialised type of flow cytometry. It provides a method for sorting a heterogenous mixture of biological cells into two or more containers, one cell at a time, based upon the specific light scattering and fluorescent characteristics of each cell. It provides quantitative recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest. In yet another embodiment, microfluidic based devices are used to evaluate PARP expression. [0216] Mass spectrometry can also be used to characterize PARP from patient samples. The two methods for ionization of whole proteins are electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). In the first, intact proteins are ionized by either of the two techniques described above, and then introduced to a mass analyser. In the second, proteins are enzymatically digested into smaller peptides using an agent such as trypsin or pepsin. Other proteolytic digest agents are also used. The collection of peptide products are then introduced to the mass analyser. This is often referred to as the "bottom up" approach of protein analysis. 102171 Whole protein mass analysis is conducted using either time-of-flight (TOF) MS, or Fourier transform ion cyclotron resonance (FT-ICR). The instrument used for peptide mass analysis is the quadrupole ion trap. Multiple stage quadrupole-time-of-flight and MALDI time-of-flight instruments also find use in this application. 102181 Two methods used to fractionate proteins, or their peptide products from an enzymatic digestion. The first method fractionates whole proteins and is called two dimensional gel electrophoresis. The second method, high performance liquid chromatography is used to fractionate peptides after enzymatic digestion. In some situations, it may be necessary to combine both of these techniques. 102191 There are two ways mass spectroscopy can be used to identify proteins. Peptide mass uses the masses of proteolytic peptides as input to a search of a database of predicted 72 masses that would arise from digestion of a list of known proteins. If a protein sequence in the reference list gives rise to a significant number of predicted masses that match the experimental values, there is some evidence that this protein is present in the original sample. [0220] Tandem MS is also a method for identifying proteins. Collision-induced dissociation is used in mainstream applications to generate a set of fragments from a specific peptide ion. The fragmentation process primarily gives rise to cleavage products that break along peptide bonds. [0221] A number of different algorithmic approaches have been described to identify peptides and proteins from tandem mass spectrometry (MS/MS), peptide de novo sequencing and sequence tag based searching. One option that combines a comprehensive range of data analysis features is PEAKS. Other existing mass spec analysis software include: Peptide fragment fingerprinting SEQUEST, Mascot, OMSSA and X!Tandem). [0222] Proteins can also be quantified by mass spectrometry. Typically, stable (e.g., non radioactive) heavier isotopes of carbon (C13) or nitrogen (N15) are incorporated into one sample while the other one is labelled with corresponding light isotopes (e.g., C12 and N14). The two samples are mixed before the analysis. Peptides derived from the different samples can be distinguished due to their mass difference. The ratio of their peak intensities corresponds to the relative abundance ratio of the peptides (and proteins). The methods for isotope labelling are SILAC (stable isotope labelling with amino acids in cell culture), trypsin-catalyzed 018 labeling, ICAT (isotope coded affinity tagging), ITRAQ (isotope tags for relative and absolute quantitation), "Semi-quantitative" mass spectrometry can be performed without labeling of samples. Typically, this is done with MALDI analysis (in linear mode). The peak intensity, or the peak area, from individual molecules (typically proteins) is here correlated to the amount of protein in the sample. However, the individual signal depends on the primary structure of the protein, on the complexity of the sample, and on the settings of the instrument. 102231 N-terminal sequencing aids in the identification of unknown proteins, confirm recombinant protein identity and fidelity (reading frame, translation start point, etc.), aid the interpretation of NMR and crystallographic data, demonstrate degrees of identity between proteins, or provide data for the design of synthetic peptides for antibody generation, etc. N terminal sequencing utilises the Edman degradative chemistry, sequentially removing amino acid residues from the N-terminus of the protein and identifying them by reverse-phase HPLC. Sensitivity can be at the level of 1 00s femtomoles and long sequence reads (20-40 residues) can often be obtained from a few I Os of picomoles of starting material. Pure 73 proteins (>90%) can generate easily interpreted data, but insufficiently purified protein mixtures may also provide useful data, subject to rigorous data interpretation. N-terminally modified (especially acetylated) proteins cannot be sequenced directly, as the absence of a free primary amino-group prevents the Edman chemistry. However, limited proteolysis of the blocked protein (e.g., using cyanogen bromide) may allow a mixture of amino acids to be generated in each cycle of the instrument, which can be subjected to database analysis in order to interpret meaningful sequence information. C-terminal sequencing is a post translational modification, affecting the structure and activity of a protein. Various disease situations can be associated with impaired protein processing and C-terminal sequencing provides an additional tool for the investigation of protein structure and processing mechanisms. Formulations, Routes of Administration, and Dosing Regimen [0224 In some embodiments are provided formulations (e.g., pharmaceutical formulations) comprising 4-iodo-3-nitrobenzamide, a metabolite thereof, or a pharmaceutically acceptable salt or solvate thereof, an antimetabolite (e.g., gemcitabine) and a platinum compound (e.g., carboplatin) and a carrier, such as a pharmaceutically acceptable carrier. The formulations may include optical isomers, diastereomers, carriers, or pharmaceutically acceptable salts of the compounds disclosed herein. In some embodiments, the carrier is a cyclodextrin, or a derivative thereof, e.g., hydroxypropyl- -- cyclodextrin (-IP3CD). In some embodiments the fornulations are formulated for intravenous administration. [02251 The pharmaceutical compositions of the present invention may be provided as a prodrug and/or may be allowed to interconvert to 4-iodo-3-nitrobenzamide form in vivo after administration. That is, either 4-iodo-3-nitrobenzamide or metabolites thereof or pharmaceutically acceptable salts may be used in developing a formulation for use in the present invention. 4-iodo-3-nitrobenzamide (or a metabolite thereof), an antimetabolite (e.g., gemcitabine) and a platinum compound (e.g., carboplatin) provided herein may be formulated in separate formulations or in the same formulation. 4-iodo-3-nitrobenzamide (or a metabolite thereof, an antimetabolite (e.g., gemcitabine) and a platinum compound (e.g., carboplatin) provided herein may be administered through different administration route or using same administration routes. [02261 A formulation may comprise both the 4-iodo-3-nitrobenzamide compound and acid forms in particular proportions, depending on the relative potencies of each and the intended 74 indication. The two forms may be formulated together or in different formulations. They may be in the same dosage unit e.g. in one cream, suppository, tablet, capsule, or packet of powder to be dissolved in a beverage; or each form may be formulated in a separate unit, e.g., two creams, two suppositories, two tablets, two capsules, a tablet and a liquid for dissolving the tablet, a packet of powder and a liquid for dissolving the powder, etc, 102271 4-iodo-3-nitrobenzamide (or a metabolite thereof), an antimetabolite (e.g., gemcitabine) and a platinum compound (eg., carboplatin) provided herein may be co administered to the patient. Co-administration is meant to include simultaneous or sequential administration of the compounds individually or in combination (more than one compound), such as described herein. 4-iodo-3-nitrobenzamide (or a metabolite thereof), an antimetabolite (e.g., gemcitabine) and/or a platinum compound (e.g., carboplatin) provided herein may be continuously or not continuously given to a patient. "Not continuously" means that the compound or composition provided herein is not administered to the patient over a period of time, e.g., there is a resting period when the patient does not receive the compound or composition. It may be that one compound is administered continuously administered to a patient while the second compound is not administered continuously administered to the patient. 102281 The pharmaceutical compositions of the 4-iodo-3-nitrobenzamide, an antimetabolite (e.g., gemcitabine) and a platinum compound (e.g, carboplatin) can be combined with other active ingredients, such as other chemotherapeutic agents as described herein. The two compounds and/or forms of a compound may be formulated together, in the same dosage unit e.g., in one cream, suppository, tablet, capsule, or packet of powder to be dissolved in a beverage; or each form may be formulated in separate units, e.g., three creams, three suppositories, three tablets, three capsules, a tablet and a liquid for dissolving the tablet, a packet of powder and a liquid for dissolving the powder, etc. [0229] The term "pharmaceutically acceptable salt" means those salts which retain the biological effectiveness and properties of the compounds used in the present invention, and which are not biologically or otherwise undesirable. For example, a pharmaceutically acceptable salt does not interfere with the beneficial effect of the compound of the invention in treating platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer). [0230] Typical salts are those of the inorganic ions, such as, for example, sodium, potassium, calcium and magnesium ions. Such salts include salts with inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, p toluenesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic 75 acid, mandelic acid, malic acid, citric acid, tartaric acid or maleic acid. In addition, where compounds contain a carboxy group or other acidic group, it may be converted into a pharmaceutically acceptable addition salt with inorganic or organic bases. Examples of suitable bases include sodium hydroxide, potassium hydroxide, ammonia, cyclohexylamine, dicyclohexyl-amine, ethanolamine, diethanolamine and triethanolamine. [0231] For injection, the 4-iodo-3-nitrobenzamide or pharmaceutically acceptable salt thereof may be formulated for administration in aqueous solutions, preferably in physiologically compatible buffers such as phosphate buffers, Hank's solution, or Ringer's solution. Such compositions may also include one or more excipients, for example, preservatives, solubilizers, fillers, lubricants, stabilizers, albumin, and the like. Formulations of 4-iodo-3-nitrobenzamide are described in US Pat. Publ. No. 2008/0176946 Al, which is incorporated by reference in its entirety, particularly with reference to intravenous (e.g., hydroxypropyl-3-cyclodextrin, etc.) and oral (e.g, sodium lauryl sulfate, etc.) formulations. In some embodiments, the 4-iodo-3-nitrobenzamide is formulated in 25% (w/v) hydroxypropyl-f3-cyclodextrin and 10 mM phosphate buffer for intravenous administration as described in U.S. Patent Application No. 12/510,969, filed July 28, 2009, which is incorporated herein by reference. 10232i Additional methods of formulation, such as for the antimetabolite (e.g., gemcitabine) and the platinum compound (e.g., carboplatin) described herein, are known in the art, for example, as disclosed in Remington's Pharmaceutical Sciences, latest edition, Mack Publishing Co., Easton, PA. Compositions described herein may also be formulated for transmucosal administration, buccal administration, for administration by inhalation, for parental administration, for transdermal administration, and rectal administration. [0233] Pharmaceutical compositions suitable for use as described herein include compositions wherein the active ingredients are present in an effective amount, i.e., in an amount effective to achieve therapeutic and/or prophylactic benefit in at least one of the platinum-resistant ovarian cancers (e.g., recurrent ovarian cancer) described herein. The actual amount effective for a particular administration will depend on the platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) being treated, the condition of the subject, the formulation, and the route of administration, as well as other factors known to those of skill in the art in view of the specific teaching provided herein. In light of the disclosure herein, optimization of an effective amount of 4-iodo-3-nitrobenzamide, antimetabolite (e.g., gemcitabine), and/or platinum compound (e.g., carboplatin) provided herein, within the ranges specified, may be determined. 76 [0234] In some embodiments, the composition is administered in unit dosage form. In some embodiments, the unit dosage form is adapted for oral or parenteral administration. In some embodiments, upon administration of the composition, at least one therapeutic effect is obtained, said at least one therapeutic effect being reduction in size of a tumor, reduction in metastasis, complete remission, partial remission, pathologic complete response, increase in overall response rate,or stable disease. In some embodiments, upon administration of the composition, an improvement of clinical benefit rate (CBR = CR + PR + SD > 6 months) is obtained as compared to treatment with the antimetabolite (e.g., gemcitabine) and the platinum compound (e.g., carboplatin) but without 4-iodo-3-nitrobenzamide or the metabolite thereof or the pharmaceutically acceptable salt thereof. In some embodiments, the improvement of clinical benefit rate is at least about 20%. In some embodiments, the improvement of clinical benefit rate is at least about 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% or more. [0235] The compositions described herein may be administered to a patient through appropriate route, such as, but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, intraarterial, subcutaneous, intranasal, epidural, and oral routes. In some embodiments, the composition or compound(s) provided herein is administered by the parenteral route, e.g., intravenously, intraperitoneally, subcutaneously, intradermally, or intramuscularly. [0236] Compositions may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered in combination with other biologically active agents, e.g., such as described herein. Administration can be systemic or local. In addition, it may be desirable to introduce the pharmaceutical compositions of the invention into the central nervous system by any suitable route, including intraventricular and intrathecal injection; intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir. [0237] The dosage of 4-iodo-3-nitrobenzamide ("BA") or a metabolite thereof or a pharmaceutically acceptable salt thereof may vary depending upon the patient age, height, weight, overall health, etc. In some embodiments, the dosage of 4-iodo-3-nitrobenzamide is in the range of about I mg/kg to about 100 mg/kg, about 2 mg/kg to about 50 mg/kg, about 2 to 10 mg/kg, about 4 to 8 mg/kg, about 5 to 7 mg/kg, about I to about 25 mg/kg, about 2 to about 70 mg/kg, about 4 to about 100 mg/kg, about 4 to about 25 mg/kg, about 4 to about 20 mg/kg, about 50 to about 100 mg/kg or about 25 to about 75 mg/kg. In some embodiments, 77 the dosage of 4-iodo-3-nitrobenzamide is about any of 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 30 mg/kg, 50 mg/kg, 75 mg/kg, or 100 mg/kg. 4-iodo-3-nitrobenzamide or its metabolite may be administered intravenously, e.g., by IV infusion over about 10 to about 300 minutes, about 30 to about 180 minutes, about 45 to about 120 minutes or about 60 minutes (i.e. about 1 hour). In some embodiments, 4-iodo-3-nitrobenzamide may alternatively be administered orally. 102381 The dosage of an antimetabolite provided herein (e.g., gemeitabine) may vary depending upon the patient age, height, weight, overall health, etc. In some embodiments, the dosage of the antimetabolite (e.g., gemcitabine) provided herein is in the range of about 10 mg/mn 2 to about 1000 mg/mi 2 , about 25mg/m 2 to about 500 mg/m 2 , about 50 mg/m 2 to about 200 mg/m2, about 75 mg/m 2 to about 200 mg/n 2 . In some embodiments, the dosage of the antimetabolite (e.g, gemcitabine) provided herein is about any of 50 mg/m2, 75 mg/mi, 100 mg/m2, 125 ng/m2, 150 mg/in2, 175 mg/m 2 , 200 mg/m 2 , 250 mg/m, or 300 mg/i 2 . An antimetabolite (e.g., gemcitabine) provided herein may be administered intravenously, e.g., by IV infusion over about 10 to about 500 minutes, about 10 to about 300 minutes, about 30 to about 180 minutes, about 45 to about 120 minutes or about 60 minutes (i.e. about 1 hour). In some embodiments, an alkylating agent provided herein may alternatively be administered orally. [0239] The dosage of a platinum compound provided herein (e.g., carboplatin) may vary depending upon the patient age, height, weight, overall health, etc. The dosage of a platinum compound, e.g., carboplatin, is determined by calculating the area under the blood plasma concentration versus time curve (AUC) in mg/mL-minute by methods known to those skilled in the cancer chemotherapy art, taking into account the patient's renal activity estimated by measuring creatinine clearance or glomerular filtration rate. In some embodiments, the dosage of carboplatin for combination treatment along with an antimetabolite (e.g., gemeitabine) and a PARP inhibitor (e.g., 4-iodo-3-nitrobenzamide) is calculated to provide an AUC of about 0.1-6 mg/ml-min, about 1-3 mg/ml-min, about 1.5 to about 2.5 mg/ml-min, about 1.75 to about 2.25 mg/mli-min or about 2 mg/ml-min. (AUC 2, for example, is shorthand for 2 mg/ml-minute). Alternatively, the dosage of platinum compound (e.g., carboplatin) is calculated based on the patient's body surface area, In some embodiments, a suitable dose of platinum compound (e.g., carboplatin) is about 10 to about 400 mg/m 2 , e.g., about 360 mg/m 2 Platinum complexes platinum compound (e g., carboplatin) are normally administered intravenously (IV) over a period of about about 10 to about 500 minutes, about 10 to about 300 minutes, about 30 to about 180 minutes, about 45 to about 120 minutes or 78 about 60 minutes. In this context, the term "about" has its normal meaning of approximately. In some embodiments, about means ±10% or ±5%. f[240] In some cases, a beneficial effect is achieved when the administration of the antimetabolite (e.g., gemcitabine) and the platinum compound (e.g., carboplatin) is temporally removed from the administration of the 4-iodo-3-nitrobenazmide (or pharmaceutically acceptable salt or solvate thereof, or metabolite thereof) by a significant period of time (e.g., about 12 hours, about 24 hours, about 36 hours, about 48 hours, etc.), or, for example, when administration is spaced apart by at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, etc.). For example, administration may be on different days of a treatment cycle, such as the treatment cycles described herein. The interval between administration of the 4-iodo-3-nitrobenzamide, the antimetabolite (e.g., gemcitabine), and the platinum compound (e.g., carboplatin) may vary within a treatment cycle (e.g., administration is not always spaced apart by 1 day, but may be at intervals of I day followed by an interval of 3 days, etc.). Similarly, at certain times during the treatment cycle, the 4-iodo -3-nitrobenzamide, the antimetabolite (e.g., gemcitabine), and the platinum compound (e.g., carboplatin) may be administered at the same time, and at other points during the treatment administered at different times. 102411 In some embodiments, the treatment includes 1 cycle, 2 cycles, 3 cycles, 4 cycles, 5 cycles, 6 cycles, 7 cycles, 8 cycles, 9 cycles or 10 cycles. As used here, the term "cycle" means "treatment cycle." In some embodiments, the treatment includes at most any of 2 cycles, 3 cycles, 4 cycles, 5 cycles, 6 cycles, 7 cycles, 8 cycles, 9 cycles, or 10 cycles. [02421 In some embodiments, the treatment comprises a treatment cycle of at least about any of I week, 10 days, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 12 weeks, or 15 weeks. 10243] 4-iodo-3-nitrobenzamide may be administered every day of the treatment cycle, or administered on certain days but not on every clay of the treatment cycle. In some embodiments, 4-iodo-3-nitrobenzamide is administered daily, once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once 10 days, once two weeks, once three weeks, once four weeks, once six weeks, or once eight weeks. 4 iodo-3-nitrobenzamide may be administered on the selected days of each treatment cycle, for example, 4-iodo-3-nitrobenzamide is administered daily for the period of 3 (or 4, 5, 6, 7, 8, 9, 10) days of the treatment cycle, and 4-iodo-3-nitrobenzamide is not administered on other days of the treatment cycle. 79 [0244] An antimetabolite (e.g., gemcitabine) provided herein may be administered daily, e.g., every day of the treatment cycle, or administered on certain days but not on every day of the treatment cycle. In some embodiments, the antimetabolite (e.g., gemcitabine) provided herein is administered daily, once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once every 10 days, once every two weeks, once every three weeks, once every four weeks, once every six weeks, or once every eight weeks. An antimetabolite (e.g., gemcitabine) provided herein may be administered on the selected days of each treatment cycle, for example, the antimetabolite (e.g., gemcitabine) is administered daily for the period of 3 (or 4, 5, 6, 7, 8, 9, 10) days of the treatment cycle, and the antimetabolite (e.g., gemcitabine) is not administered on other days of the treatment cycle. [02451 A platinum compound (e.g., carboplatin) provided herein may be administered daily, e.g., every day of the treatment cycle, or administered on certain days but not on every day of the treatment cycle. In some embodiments, the platinum compound (e.g., carboplatin) provided herein is administered daily, once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once every 10 days, once every two weeks, once every three weeks, once every four weeks, once every six weeks, or once every eight weeks. A platinum compound (e.g., carboplatin) provided herein may be administered on the selected days of each treatment cycle, for example, the platinum compound (e.g., carboplatin) is administered daily for the period of 3 (or 4, 5, 6, 7, 8, 9, 10) days of the treatment cycle, and the platinum compound (e.g., carboplatin) is not administered on other days of the treatment cycle. [02461 In some embodiments of any one of the methods for treating platinum-resistant recurrent ovarian cancer provided herein, the method comprises 6 or fewer dosing cycles, wherein each cycle contains a period of 21 days. In some embodiments, 4-iodo-3 nitrobenzamide or the pharmaceutically acceptable salt thereof is administered at about 5.1 mg/kg to about 8.6 mg/kg on days 1, 4, 8, and 11 of each cycle, the antimetabolite (e.g., gemcitabine is administered at 1000 mg/m 2 daily on days 1 and 8 of each cycle, and the platinum compound (e.g., carboplatin) is administered at 4 mg/mleminute (AUC 4) on day I of each cycle. 80 Kits [0247] Also provided are kits for administration of 4-iodo-3-nitrobenzamide or a metabolite thereof or a pharmaceutically acceptable salt thereof, gemcitabine and carboplatin as provided herein. [0248J In certain embodiments the kits may include a dosage amount of at least one composition as disclosed herein. Kits may further comprise suitable packaging and/or instructions for use of the formulation. Kits may also comprise a means for the delivery of the formulation thereof. [0249] The kits may include other pharmaceutical agents (such as the side-effect limiting agents, chemotherapy agents, gene therapy agents, DNA therapy agents, RNA therapy agents, viral therapy agents, nanotherapy agents, small molecule enzymatic inhibitors, anti-metastatic agents, etc.), for use in conjunction with 4-iodo-3-nitrobenzamide or a metabolite thereof or a pharmaceutically acceptable salt thereof, an antimetabolite (e.g., gemcitabine) provided herein, and a platinum compound (e.g., carboplatin) provided herein. These agents may be provided in a separate form, or mixed with 4-iodo-3-nitrobenzamide or a metabolite thereof or a pharmaceutically acceptable salt thereof, an antimetabolite (e.g., gemcitabine) provided herein, and a platinum compound (e.g., carboplatin) provided herein, provided such mixing does not reduce the effectiveness of 4-iodo-3-nitrobenzamide (or a metabolite thereof or a pharmaceutically acceptable salt thereof), an antirmetabolite (e.g., gemcitabine) provided herein or a platinum compound (e.g., carboplatin) provided herein, and is compatible with the route of administration. Similarly, the kits may include additional agents for adjunctive therapy or other agents known to the skilled artisan as effective in the treatment or prevention of platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) described herein. [0250] The kits may optionally include appropriate instructions for preparation and administration of the composition, side effects of the composition, and any other relevant information. The instructions may be in any suitable format, including, but not limited to, printed matter, videotape, computer readable disk, optical disc or directions to internet-based instructions. [02511 In another aspect, provided are kits for treating a patient who suffers from or is susceptible to the platinum-resistant ovarian cancer (e.g., recurrent ovarian cancer) described herein, comprising a first container comprising a dosage amount of a formulation as disclosed herein, and instructions for use. The container may be any of those known in the art and appropriate for storage and delivery of intravenous formulation. In certain embodiments the 8i kit further comprises a second container comprising a pharmaceutically acceptable carrier, diluent, adjuvant, etc. for preparation of the composition to be administered to the patient. [02521 Kits may also be provided that contain sufficient dosages of the inhibitor (including formulation thereof) as disclosed herein to provide effective treatment for a patient for an extended period, such as 1-3 days, 1-5 days, a week, 2 weeks, 3, weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months or more. [0253] Kits may also include multiple doses of the compounds and instructions for use and packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies. [0254] The kits may include the compounds as described herein packaged in either a unit dosage form or in a multi-use form, The kits may also include multiple units of the unit dose form. In certain embodiments, provided are the compound described herein in a unit dose form. In other embodiments the compositions may be provided in a multi-dose form (e.g., a blister pack, etc.). [0255] The examples below are intended to be purely exemplary of the invention and should therefore not be considered to limit the invention in any way. The following examples and detailed description are offered by way of illustration and not by way of limitation. Additional examples can be found in U.S. Patent Publication No. US 2009/0123419 A1, which is incorporated herein by reference. EXAMPLES Example 1: Phase lB study of 4-iodo-3-nitrobenzamide in combination with chemotherapy in patients with advanced solid tumors. [0256] A Phase Ib, open-label, dose escalation study evaluates the safety of 4-iodo-3 nitrobenzamide (BA) (2.0, 2.8, 4.0, 5.6, 8.0, and 11.2 mg/kg) in combination with chemotherapeutic regimens (topotecan, gemcitabine, temozolomide, and carboplatin + paclitaxel) in subjects with advanced solid tumors including ovarian tumors. The dose escalation phase of the study has been completed, and well tolerated combinations of 4-iodo 3-nitrobenzamide and cytotoxic chemotherapy have been identified. The protocol has been amended to evaluate 4-iodo-3-nitrobenzamide in combination with chemotherapy in specific tumor types. 10257] Rationale. Topotecan targets topoisomerase I, which plays a critical role in DNA replication, transcription, and Recombination. Topotecan selectively stabilizes topoisomerase 82 I-DNA covalent complexes, inhibiting re-ligation of topoisomerase I-mediated single-strand DNA breaks and producing lethal double-strand DNA breaks. Poly(ADP-Ribose) Polymerase-1 (PARP-1) interacts with topoisomerase I and increases tumor sensitivity to topoisomerase 1 inhibitors. Preclinical studies show that the PARPI inhibitor 4-iodo-3 nitrobenzamide potentiates the antitumor activity of topotecan. PARP 1 is significantly up regulated in human primary ovarian tumors. [02581 Study Design. 4-iodo-3-nitrobenzamide plus cytotoxic chemotherapy (CTX) - CTX Dosing: - Topotecan: 1.5 mg/m 2 or 1.1 mg/m 2 QD for 5 days of 21 day cycle - Temozolomide: 75 mg/n 2 P.O. QD for 21 days of 28 day cycle - Gemcitabine: 1000 mg/m 2 as 30 min, infusion QW; 7 of 8 weeks; initial 28 days for safety evaluation - Carboplatin/Paclitaxel: C= AUC of 6; Pxl = 200 mg/m 2 ; both on day 1 of 21 day cycle - 4-iodo-3-nitrobenzanide Dosing: - Twice weekly; iv. infusion - Standard 3 + 3 design for 4-iodo-3-nitrobenzamide close escalation - Dose levels studied: 2.0, 2.8, 4.0, 5.6, 8.0, and up to 11.2 mg/kg Study Endpoints: - Safety, tolerability and MTD of each combination - Clinical response via RECIST every 2 cycles General Eligibility: - Subjects >18 years old with a refractory, advanced solid tumor, ECOG PS of<= 2, and adequate hematological, renal, and hepatic function - No restriction on number of prior chemotherapeutic regimens [02591 Efficacy. In terms of efficacy, 53 of 66 subjects demonstrate some clinical benefit (Table 1). 83 Table 1: Clinical Results 1 CR - ovarian; 6 R - 2 breast, 1 uterine, 1 ovarian, I renal, I sarcoma; 4 SD >= 6 cycles I adenocareinosaroma, 1 ACUP, 2 sarcoma; 42 SD > 2 cycles- multiple tumor types [0260] Ovarijan cancer patient r-esponse. As shown in Figure 1, a patient with advanced ovarian cancer has a partial response after 4 cycles of 4-iodo-3-nitrobenza1nide in a combination with topotecan. Liver lesion (target lesion) shrinksfrom 4.6 cm to 15 cm. CA 27-29 biomarker also reduces from >300 to <200. [0261] Preparation of peripheral blood lymphocyte and tumor samples. Whole blood is collected into EDTA vacutainers and human PBMCs are obtained by BD VacutainerTM CPTIiT Cell Preparation kit according to the manufacturer's instructions (BD VacutainerTM, REF 362760). Tumor samples are collected in a sterile container and placed immediately on ice. Within 30 minutes, tumor samples are snap-frozen in liquid nitrogen and stored at -80'C until homogenized for analysis. The specimen is defrosted on ice and the wet weight is documented. The tissue is homogenized using isotonic buffer [7 mmol/L HEPES, 26 mmol/L. KCl, 0.1 mmol/L dextran, 0.4 mmol/L EGTA, 0.5 mmol/L MgCl2, 45 mmol/L sucrose (pH1 7.8)]. The homogenate is kept on ice throughout the process, and homogenization is done in 10-second bursts to prevent undue warming of the sample. Unless assayed on the day of homogenization, samples are refrozen to -80'C and stored at this temperature until analyzed. 10262] Poly(ADP-ribose) polymerase assay procedure. Cell preparations are defrosted rapidly at room temperature and washed twice in ice-cold PBS. The cell pellets are resuspended in 0.15 mg/mI. digitonin to a density of 1 x 106 to 2 x 106 cells/mL for 5 minutes to permeabilize the cells (verified by trypan blue staining), following which 9 volumes of ice cold isotonic buffer are added and the sample is placed on ice. Maximally stimulated PARP activity is measured in replicate samples of 20,000 cells in a reaction mixture containing 350 mmol/L NAD+ and 10 mg/mL oligonucleotide in a reaction buffer of 100 mmol/f. Tris-H1C, 84 120 mmol/L MgCI2 (pH 7.8) in a final volume of 100 iL as described in US Patent Publication No. US 2009/0123419 Al (which is incorporated herein by reference) at 26 0 C in an oscillating water bath. The reaction is stopped after 6 minutes by the addition of excess PARP inhibitor (400 pL of 12.5 pmol/L AGO 14699) and the cells are blotted onto a nitrocellulose membrane (Hybond-N, Amersham) using a 24-well manifold. Purified PAR standards are loaded onto each membrane (0-25 pmol monomer equivalent) to generate a standard curve and allow quantification. Overnight incubation with the primary antibody (1:500 in PBS + 0.05% Tween 20 + 5% milk powder) at 4C is followed by two washes in PBS-T (PBS + 0.05% Tween 20) and then incubation in secondary antibody (1:1,000 in PBS + 0.05% Tween 20 + 5% milk powder) for 1 hour at room temperature. The incubated membrane is washed frequently with PBS over the course of 1 hour and then exposed for I minute to enhanced chemiluminescence reaction solution as supplied by the manufacturer. Chemiluminesence detected during a 5-minute exposure is measured using a Fuji LAS3000 UV Illuminator (Raytek, Sheffield, United Kingdom) and digitized using the imaging software (Fuji LAS Image version 1.1, Raytek). The acquired image is analyzed using Aida Image Analyzer (version 3.28.001), and results are expressed in LAU/mm2. Three background areas on the exposed blot are measured and the mean of the background signal from the membrane is subtracted from all results. The PAR polymer standard curve is analyzed using an unweighted one-site binding nonlinear regression model and unknowns read off the standard curve so generated. Results are then expressed relative to the number of cells loaded. Triplicate quality control samples of 5,000 L1210 cells are run with each assay, all samples from one patient being analyzed on the same blot. Tumor homogenates are assayed in a similar manner; however, the homogenization process introduces sufficient DNA damage to maximally stimulate PARP activity and oligonucleotide is not therefore required. The protein concentration of the homogenate is measured using the BCA protein assay and Titertek Multiscan MCC/340 plate reader. Results are expressed in terms of pmol PAR formed/mg protein. [0263] Evaluation of peripheral blood mononuclear cells (PBMCs) from patients shows significant and prolonged PARP inhibition after multiple (losing with 4-iodo-3 nitrobenzamide doses of 2.8 mg/kg or higher (Figure 2). 102641 Well-tolerated combinations of 4-iodo-3-nitrobenzamide and cytotoxic chemotherapy are identified. Any toxicities observed are consistent with known and expected side effects of each chemotherapeutic regimen. There is no evidence that the addition of 4 iodo-3-nitrobenzamide to any tested cytotoxic regimen either potentiates known toxicities or 85 increases the frequency of their expected toxicities. A biologically relevant dose (2.8 mg/kg) that elicits significant and sustained PARP inhibition at effective preclinical blood concentrations is identified. Approximately 80% of subjects demonstrate evidence of stable disease for 2 cycles of treatment or more, indicating potential clinical benefit. The observed pattern of tumor response is consistent with PARP expression and/or synergy with chemotherapeutic agents. Example 2: Phase II study of 4-iodo-3-nitrobenzamide in combination with gemcitabine and carboplatin in platinum-resistant recurrent ovarian cancer. [0265] A Phase II trial to evaluate the efficacy of 4-iodo-3-nitrobenzamide (BA) in combination with gemcitabine and carboplatin in the treatment of platinum-resistant recurrent ovarian cancer is currently being conducted. Platinum-resistance is defined by relapse or recurrence of ovarian cancer two to six months after receiving the last dose of a platinum based chemotherapeutic. [02661 Primary Endpoint: To evaluate the objective response rate (ORR) of gemcitabine/carboplatin in combination with 4-iodo-3 -nitrobenzamide [ Time Frame: Until progressive disease or death ]. [0267] Secondary Endpoints: (1) To determine the nature and degree of toxicity of gemcitabine/carboplatin in combination with 4-iodo-3-nitrobenzamide [ Time Frame: 30 days after last BSI-201 exposure ]; (2) To evaluate progression-free survival (PFS) of gemcitabine/carboplatin in combination with 4-iodo-3-nitrobenzamide [Time Frame: until progressive disease or death ]. [0268] Inclusion Criteria: (1) At least 18 years of age; (2) Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma; (3) Completion of only one previous course of chemotherapy which contained a platinum therapy, with resistance to that regimen. "Platinum-resistance" is defined by a relapse within 2 to 6 months after termination of platinum-based chemotherapy; (4) Measurable disease, defined by at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded), and is 20 mm when measured by conventional techniques (palpation, plain x-ray, computed tomography [CT], or magnetic resonance imaging [MRI]) or > 10 mm when measured by spiral CT; (5) Adequate organ function defined as: absolute neutrophil count (ANC) > 1,500/mm3, platelets > 100,000/mm3, creatinine clearance > 50mL/m in, alanine aminotransferase (ALT) and aspartate 86 aminotransferase (AST) < 2.5 x upper limit of normal (ULN; or < 5 x ULN in case of liver metastases); total bilirubin < 1.5 mg/dL; (6) For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy; (7) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2; and (8) Signed, institutional review board (IRB) approved written informed consent. [0269] Exclusion Criteria: (1) Concurrent invasive malignancy, not including: (i) Non melanomatous skin cancer; (ii) In situ malignancies; (iii) Concurrent superficial endometrial carcinoma, if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium); (iv) Low risk breast cancer (localized, non-inflammatory) treated with curative intent; (v) Lesions identifiable only by positron emission tomography (PET); (vi) Prior treatment with poly (ADP-ribose) polymerase (PARP) inhibitors, including BSI-201; (vii) Major medical conditions that might affect study participation (i.e., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection); (viii) Other significant co-morbid condition which the investigator feels might compromise effective and safe participation in the study, including a history of congestive cardiac failure or an electrocardiogram (ECG) suggesting significant conduction defect or myocardial ischemia; (ix) Enrollment in another investigational device or drug study, or current treatment with other investigational agents; (x) Concurrent radiation therapy to treat primary disease throughout the course of the study; (xi) Inability to comply with the requirements of the study; (xii) Pregnancy or lactation; and (xiii) Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. [0270] A maximum of 48 patients with platinum-resistant recurrent ovarian cancer will be treated in this study using a Simon two-stage design. The primary endpoint is an improved overall response rate compared to patients receiving treatment with gemeitabine and carboplatin alone determined using historical data from a previous trial. The secondary endpoints are improved progression-free survival and patient safety. The exploratory endpoints are BRCA status and translational medicine. [0271] During the first stage, study participants (n=23) received 4-iodo-3-nitrobenzamide intravenously at a dose of 5.6 mg/kg on days 1, 4, 8, and 11 of each cycle, gemcitabine at a dose of 1000 mg/n 2 on days 1 and 8 of each cycle, and carboplatin at AUC 4 (i.e., at 4 mg/ml-minute) on day I of each cycle. 87 [02721 Fourteen patients have been enrolled in this trial to date. The combination therapy was well-tolerated, with low grade nausea the most common side effect. After a minimum of four cycles/twelve weeks, the overall response rate was 21%, with 8 of 14 patients having stable disease and 3 of 14 in either complete or partial remission. Median follow-up will be performed at twelve weeks. Patients will continue with additional cycles of treatment as long as they have stable or responding disease (per RECIST criteria) and wish to remain on study. A minimum of 4 responses at the first stage of the trial are required before proceeding to the second stage (n=25). [0273] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. 10274] In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form any part of the common general knowledge in the art. [0275] The term "comprising" as used in this specification and claims means "consisting at least in part of". When interpreting statements in this specification and claims which includes the "comprising", other features besides the features prefaced by this term in each statement can also be present. Related terms such as "comprise" and "comprised" are to be interpreted in similar manner. 88

Claims (3)

1. A method of treating platinum-resistant recurrent ovarian cancer in a patient, comprising administering to the patient having ovarian cancer an effective amount of: (i) 4 iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof; (ii) gemeitabine; and (iii) carboplatin.

2. The method of claim 1, wherein the effective amount is administered over a

21-day treatment cycle, wherein (i) the effective amount of carboplatin is administered to the patient at 4 mg/mlominute (AUC 4) on day 1 of the treatment cycle; (ii) the effective amount of gemcitabine is administered to the patient at a dose of 1000 mg/m 2 on days I and 8 of the treatment cycle; and (iii) the effective amount of 4-iodo-3-nitrobenzamide or a metabolite or a pharmaceutically acceptable salt thereof is administered to the patient at a dose of 5.6 mg/kg twice weekly on days 1, 4, 8, and 11 of the treatment cycle. 3. The method of claim 2, wherein the effective amount produces at least one therapeutic effect selected from the group consisting of reduction in size of an ovarian tumor, reduction in metastasis, complete remission, partial remission, stable disease, increase in overall response rate, or a pathologic complete response. 4. The method of claim 2, wherein a comparable clinical benefit rate (CBR = CR (complete remission) + PR (partial remission) + SD (stable disease) > 6 months) is obtained compared to treatment with said gemcitabine and said carboplatin administered without 4 iodo-3-nitrobenzamide. 5. The method of claim 4, wherein the improvement of clinical benefit rate is about 20% or higher. 6. The method of claim 3, wherein the therapeutic effect is an increase in overall response rate. 7. The method of claim 6, wherein the overall response rate is greater than 15%. 8. The method of claim 6, wherein the overall response rate is greater than 20%. 9. The method of claim 6, wherein the overall response rate is greater than 30%. 10. The method of claim 1, further comprising surgery, radiation therapy, chemotherapy, gene therapy, DNA therapy, viral therapy, RNA therapy, DNA therapy, 89 adjuvant therapy, neoadjuvant therapy, immunotherapy, nanotherapy or a combination thereof 11. The method of claim 1, further comprising administering to the patient gamma irradiation. 12. The method of claim 1, wherein the platinum-resistant recurrent ovarian cancer is selected from the group consisting of epithelial, germ cell, and stromal cell tumors. 13. The method of claim 1, wherein the platinum-resistant recurrent ovarian cancer is metastatic. 14. A method as claimed in claim 1, substantially as herein described with reference to any example thereof. 15. Any invention described or claimed herein. 90