WO2012121324A1 - Méthode de sélection d'un groupe efficace de traitements anticancéreux combinant l'utilisation de trois agents, à savoir un agent anticancéreux à base de taxane, un agent anticancéreux à base d'un complexe de platine et un agent anticancéreux à base de fluorure de pyrimidine - Google Patents

Méthode de sélection d'un groupe efficace de traitements anticancéreux combinant l'utilisation de trois agents, à savoir un agent anticancéreux à base de taxane, un agent anticancéreux à base d'un complexe de platine et un agent anticancéreux à base de fluorure de pyrimidine Download PDF

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WO2012121324A1
WO2012121324A1 PCT/JP2012/055948 JP2012055948W WO2012121324A1 WO 2012121324 A1 WO2012121324 A1 WO 2012121324A1 JP 2012055948 W JP2012055948 W JP 2012055948W WO 2012121324 A1 WO2012121324 A1 WO 2012121324A1
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gene
anticancer agent
cancer
seq
platinum complex
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PCT/JP2012/055948
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Japanese (ja)
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哲治 高山
晋志 北村
えり子 青柳
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国立大学法人徳島大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the present invention relates to a method for selecting an effective group for cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent, and a taxane anticancer agent.
  • the present invention relates to a reagent for predicting the effect of cancer treatment using a combination of cancer, platinum complex anticancer agent, and fluoropyrimidine anticancer agent.
  • Surgical therapy, drug therapy (chemotherapy), etc. are known as cancer treatment methods.
  • Surgery is a treatment that removes cancerous tissue, and is effective when the degree of cancer progression is low or when no cancer metastasis is observed.
  • it is difficult to completely remove the cancer tissue when the cancer is highly advanced, when cancer metastasis is observed, or when there is a possibility of cancer metastasis. Therefore, a treatment method combining surgery and drug therapy, or a treatment method using only drug therapy is required.
  • Anticancer agents generally act on DNA synthesis or some DNA function, and exert anticancer effects by suppressing the growth of cancer cells or killing cancer cells. Thus, since the anticancer agent acts on the function that cells in the living body have universally, it can also act on normal cells and cause side effects in the living body.
  • cancers are diverse due to differences in genetic predisposition of patients, and it is known that there are patient groups in which administration of specific anticancer drugs is effective and patient groups ineffective. Therefore, administering or continuing to administer an anticancer drug to a patient for whom the administration of the anticancer drug is not effective leads to a decrease in the patient's quality of life due to the above-mentioned side effects. This leads to an increase in the cost of treatment, which is not preferable. In view of such a situation, development of methods for selecting patient groups for which treatment with various anticancer agents is effective and development of effect prediction markers are being promoted.
  • Patent Document 1 discloses that the expression level of PDGFB gene tends to be relatively high in prostate cancer cells having resistance to docetaxel, which is a taxane anticancer agent, and treatment with docetaxel. It describes that the expression level of the PDGFB gene can be used as an index in the method for selecting an effective group.
  • Non-patent document 1 discloses that the expression level of the PDGFB gene tends to be relatively high in liver cancer cells having resistance to cisplatin, which is a platinum complex anticancer agent, and cisplatin. It describes that the expression level of the PDGFB gene can be used as an index in the method for selecting an effective treatment group.
  • Non-Patent Document 2 states that the expression level of ATP7B gene tends to be relatively low in colorectal cancer cells resistant to fluorouracil, which is a fluoropyrimidine anticancer agent, and It is described that the expression level of the ATP7B gene can be used as an index in the method for selecting an effective group for treatment with fluorouracil.
  • the present invention relates to a method for selecting an effective group for cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent, and a taxane anticancer agent.
  • An object of the present invention is to provide a reagent for predicting the effect of cancer treatment using a combination of cancer, platinum complex anticancer agent, and fluoropyrimidine anticancer agent.
  • the effective group can be selected using the expression level of the specific gene as an index, as described in Patent Document 1 and Non-Patent Documents 1 and 2 above. It is known. Specifically, the expression level of PDGFB gene is relatively low in the effective group of taxane anticancer agents, and the expression level of PDGFB gene is relatively low in the effective group of platinum complex anticancer agents. It is known that the expression level of ATP7B gene is relatively high in the effective group of fluoropyrimidine anticancer agents.
  • the expression level of the same gene can be used as an index, and further, there is a difference between the expression level in the effective group and the expression level in the ineffective group. It is not known at all whether or not it shows a similar tendency.
  • the present inventors in an effective group of cancer treatments using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent, Compared to the ineffective group, the expression level of PDGFB gene and JMJD2A gene tends to be high, and PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, It was found that the expression levels of STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene tend to be low.
  • the tendency that the expression level of PDGFB gene tends to be higher in the effective group than in the non-effective group is that when the taxane anticancer agent and the platinum complex anticancer agent are used alone ( The tendency was the opposite of Patent Document 1 and Non-Patent Document 1).
  • the fact that the expression level of the ATP7B gene tends to be lower in the effective group than in the non-effective group was the reverse tendency when the fluorinated pyrimidine anticancer agent was used alone (Non-patent Document 2). .
  • the present inventors have conducted further earnest research, and as a result, PDGFB gene, PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A
  • a taxane anticancer agent, a platinum complex anticancer agent using as an index the amount of the expression product of at least one gene selected from the group consisting of the gene, STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene, And it discovered that the effective group of the cancer treatment which used together 3 types of fluorinated pyrimidine type
  • the present invention has the following configuration.
  • a gene for measuring the amount of expression product in step (a) is: (I) PDGFB gene, or (ii) PDGFB gene, and PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, EGR1 gene, Item 2.
  • Item 2 Genes for measuring the amount of expression product in step (a) are PDGFB gene and PCGF3 gene, and CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX Item 3.
  • Item 3 Item 1 or 2 characterized in that the gene for measuring the amount of expression product in the step (a) is PDGFB gene, PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, and PLK2 gene. the method of.
  • Item 4 Items 1 to 3, wherein the taxane anticancer agent is docetaxel, the platinum complex anticancer agent is cisplatin, or the fluoropyrimidine anticancer agent is tegafur. 4. The method according to any one of 3.
  • Item 5 Items 1 to 3, wherein the taxane anticancer agent is docetaxel, the platinum complex anticancer agent is cisplatin, and the fluoropyrimidine anticancer agent is tegafur. 4. The method according to any one of 3.
  • Item 6 The method according to any one of Items 1 to 5, wherein the cancer is stomach cancer.
  • a probe or primer comprising a polynucleotide having a base sequence of 15 bases or longer that specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15 ,
  • Probe or primer is (I) a probe or primer comprising a polynucleotide having a base sequence of 15 bases or longer, which specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in SEQ ID NO: 1, or (II ) Probes or primers comprising a polynucleotide having a base sequence of 15 bases or longer and specifically hybridizing with a continuous base sequence of at least 15 bases in the base sequence shown in SEQ ID NO: 1 and SEQ ID NOs: 2 to 15 A probe or primer consisting of a polynucleotide having a base sequence of 15 bases or more, which specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any one of Item 8. The reagent according to Item 7.
  • Item 8-2 Antibody (III) an antibody that recognizes a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 16, or (IV) an antibody that recognizes a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 16, and any one of SEQ ID NOs: 17 to 30 An antibody that recognizes a polypeptide consisting of the amino acid sequence shown in Item 9.
  • Item 9 Item 7 or wherein the taxane anticancer agent is docetaxel, the platinum complex anticancer agent is cisplatin, or the fluoropyrimidine anticancer agent is tegafur. 9. The reagent according to any one of 8.
  • Item 10 Item 7 or, wherein the taxane anticancer agent is docetaxel, the platinum complex anticancer agent is cisplatin, and the fluoropyrimidine anticancer agent is tegafur. 9. The reagent according to any one of 8.
  • Item 11 The reagent according to any one of Items 7 to 10, wherein the cancer is gastric cancer.
  • a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more, which specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15; Use for predicting the effects of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more, which specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15; Use as a reagent for predicting the effects of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more, which specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15; Use for the manufacture of a reagent for predicting the effect of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • Item 15 An antibody that recognizes a polypeptide consisting of the amino acid sequence represented by any of SEQ ID NOs: 16 to 30; Used to predict the effects of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • Item 16 An antibody that recognizes a polypeptide consisting of the amino acid sequence represented by any of SEQ ID NOs: 16 to 30; Use as a reagent for predicting the effects of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • Item 17 An antibody that recognizes a polypeptide consisting of the amino acid sequence represented by any of SEQ ID NOs: 16 to 30; Use for the manufacture of a reagent for predicting the effect of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • an effective group for cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent is selected with high probability.
  • Can do Furthermore, it consists of PDGFB gene and PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene
  • the effective group can be selected with higher probability.
  • cancer treatment is actively performed using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent. Can lead to recovery of the patient's cancer.
  • a taxane anticancer agent for patients who were not selected as effective groups, that is, non-effective groups, a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent were used in combination. Therefore, it is possible to perform another treatment method that is more effective for the patient group without actively performing the cancer treatment. This is effective in terms of both reducing the side effects that may occur due to the administration of the anticancer agent and reducing the increase in the cost of treatment caused by unnecessary (ineffective) treatment.
  • the screening method of the present invention is effective for cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent. This is a method for selecting a group, and includes steps (a), (b), and (c) described later.
  • Selection targets according to the selection method of the present invention include taxane anticancer agents, platinum complex anticancer agents, and fluoropyrimidine anticancer agents. It is an effective group for cancer treatment using 3 types in combination.
  • the cancer type is a cancer type capable of performing cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • a taxane anticancer agent for example, but not limited to, stomach cancer, liver cancer, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, endometrial cancer, ovarian cancer, esophageal cancer, lung cancer, head and neck
  • examples include cancer, breast cancer, biliary tract cancer, bile duct cancer, and prostate cancer.
  • stomach cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, prostate cancer, and cervical cancer are preferable, and stomach cancer, esophageal cancer, head and neck cancer are preferable.
  • stomach cancer is particularly preferable.
  • degree of progression of cancer cancer that is preferably classified as a degree of progression of stage III or higher, more preferably cancer that is classified as stage IV.
  • the treatment method is a cancer treatment method using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • taxane-based anticancer agents examples include docetaxel, paclitaxel (taxol), taxadiene, baccatin III, taxinin A, breviforiol, taxapine D, and the like. From the viewpoint of accuracy of the screening method of the present invention, docetaxel Or paclitaxel is preferred, and docetaxel is more preferred.
  • the dose of the taxane anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • platinum complex anticancer agent examples include cisplatin, carboplatin, nedaplatin, and oxaliplatin, and cisplatin is preferable from the viewpoint of accuracy of the screening method of the present invention.
  • the dose of the platinum complex anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • Examples of the fluorinated pyrimidine anticancer agent include tegafur, fluorouracil, and flucytosine. From the viewpoint of accuracy of the screening method of the present invention, tegafur or fluorouracil is preferable, and tegafur is more preferable.
  • tegafur is used as the fluoropyrimidine anticancer agent, it is preferable to use gimeracil and oteracil potassium together, and the molar ratio of tegafur: gimeracil: oteracil potassium is, for example, 0.5-2: 0.
  • the dose of the fluorinated pyrimidine anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • the treatment mode of the combined cancer treatment is particularly limited as long as it is a known method as a treatment mode of administering all of the fluoropyrimidine anticancer agent, the taxane anticancer agent, and the platinum complex anticancer agent.
  • a treatment schedule of about 1 to 4 weeks is set as one course, and this course is repeated a plurality of times.
  • the treatment schedule is such that the fluoropyrimidine anticancer agent is used for a certain period, preferably 7 to 28 days, more preferably 10 to 21 days, still more preferably 12 to After daily administration for 16 days, an anticancer agent non-administration period is set for a certain period, preferably 4 to 10 days, more preferably 6 to 8 days.
  • group anticancer agent in any one of these is mentioned.
  • the target to be selected by the selection method of the present invention is a patient group in which a treatment method using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent is effective. . More specifically, when a combination treatment of the above three anticancer agents is actually performed, preferably when the above course of treatment is repeated a plurality of times, the cancer area is reduced, or cancer This is a group of patients with a downstage.
  • the effective group is more preferably a patient group having a tumor reduction rate of 3% or more, more preferably 6% or more, particularly preferably 10% or more when the above course of treatment is actually performed once.
  • Step (a) of the present invention comprises a PDGFB gene, a PCGF3 gene, a CISH gene, an ANXA5 gene, an ANTXR2 gene, a B4GALT5 gene, a PLK2 gene, an ATP7B gene, a FAM116A gene in a biological sample containing cancer tissue of a cancer patient, This is a step of measuring the amount of an expression product of at least one gene selected from the group consisting of HECA gene, JMJD2A gene, STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene.
  • the biological sample is not particularly limited as long as it contains cancer tissue of a cancer patient, and depending on the type of cancer, body fluid (blood, urine, etc.), tissue, extract thereof, and culture of collected tissue, etc. Is mentioned.
  • the collection method of a biological sample can be suitably selected by a method according to the type of biological sample and the cancer type.
  • the genes to be measured in the step (a) are PDGFB gene, PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, EGR1 gene, AVPI1 A gene and at least one gene selected from the group consisting of the ERLIN1 gene.
  • the gene to be measured in step (a) is preferably (I) PDGFB gene, or (ii) PDGFB gene, and PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, EGR1 gene, Examples include at least one gene selected from the group consisting of the AVPI1 gene and the ERLIN1 gene.
  • the gene to be measured in the step (a) is more preferably from the viewpoint of accuracy of the selection method of the present invention, (Iii) PDGFB gene and PCGF3 gene, or (iv) PDGFB gene and PCGF3 gene, and CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, Examples thereof include at least one gene selected from the group consisting of EGR1 gene, AVPI1 gene, and ERLIN1 gene.
  • the gene to be measured in the step (a) is more preferably (V) PDGFB gene, PCGF3 gene, and CISH gene, or (vi) PDGFB gene, PCGF3 gene, and CISH gene, and ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A
  • Examples include at least one gene selected from the group consisting of a gene, a STYX gene, an EGR1 gene, an AVPI1 gene, and an ERLIN1 gene.
  • the gene to be measured in the step (a) is more preferably from the viewpoint of the accuracy of the selection method of the present invention, (Vii) PDGFB gene, PCGF3 gene, CISH gene, and ANXA5 gene, or (viii) PDGFB gene, PCGF3 gene, CISH gene, and ANXA5 gene, and ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA Examples include at least one gene selected from the group consisting of a gene, JMJD2A gene, STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene.
  • the genes to be measured in the step (a) are still more preferably PDGFB gene, PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, and PLK2 gene from the viewpoint of accuracy of the selection method of the present invention.
  • the gene to be measured in the step (a) is particularly preferably a PDGFB gene, a PCGF3 gene, a CISH gene, an ANXA5 gene, an ANTXR2 gene, a B4GALT5 gene, a PLK2 gene, an ATP7B gene, from the viewpoint of the accuracy of the selection method of the present invention.
  • the expression product of the gene to be measured is mRNA transcribed from the gene sequence of the gene to be measured or a protein translated from the mRNA.
  • the measurement method of the gene expression product is not particularly limited as long as it can measure the amount of mRNA or protein, and a known measurement method can be used. Examples of such measurement methods include measuring the amount of mRNA, for example, PCR method, RT-PCR method, Northern blot method, in-situ hybridization method, microarray method, etc. Examples include Western blotting and immunostaining. A biological sample is prepared by performing an appropriate process according to these measurement methods.
  • the reagent according to the present invention described later can be used as a reagent containing a primer, a probe, or an antibody.
  • Step (b) The step (b) of the present invention comprises the amount of the expression product obtained in the step (a) (hereinafter collectively referred to as “gene expression level”), a taxane anticancer agent, and a platinum complex anticancer.
  • gene expression level the expression product obtained in the step (a)
  • control gene expression level the amount of the corresponding gene expression product in the non-effective group of cancer treatments combined with three types of drugs and fluoropyrimidine anticancer agents
  • the ineffective group of cancer treatments using a combination of taxane anticancer agent, platinum complex anticancer agent, and fluoropyrimidine anticancer agent is effective as a treatment method using the above three types in combination.
  • This is a group of patients that are not. More specifically, it is a patient group in which reduction of the cancer site or cancer downstage was not observed as a result of repeating the above-described treatment course a plurality of times.
  • the ineffective group is more preferably a patient group in which the tumor reduction rate is less than 3%, more preferably less than 6%, and particularly preferably less than 10% as a result of performing the above-mentioned treatment course once.
  • the amount of the corresponding gene expression product in the ineffective group is the amount of the expression product in the ineffective group of the same gene as that measured in the step (a). That is, when the amount of the gene expression product measured in step (a) is the amount of the PDGFB gene expression product, the amount of the corresponding gene expression product is a cancer that is known to be an ineffective group. It is the amount of the expression product of the PDGFB gene in a biological sample containing cancer tissue of a patient.
  • the comparison method is not particularly limited as long as the amount of the gene expression product can be compared, and can be appropriately selected according to the measurement method of the gene expression product.
  • Step (c) Step (c) of the present invention is a step of determining the cancer patient as an effective group when the following criteria (A) and (B) are satisfied.
  • Reference (A) means that when the measured gene is a PDGFB gene or JMJD2A gene, the gene expression level is higher than the control gene expression level.
  • Reference (B) means that the measured gene is PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, STYX gene, EGR1 gene, AVPI1 gene, or In the case of the ERLIN1 gene, the gene expression level is lower than the control gene expression level.
  • step (c) when the genes whose expression products are measured in step (a) are the PDGFB gene and the PCGF3 gene, in step (c), the PDGFB gene expression level is higher than the PDGFB gene control gene expression level. And when the gene expression level of the PCGF3 gene is lower than the gene expression level of the PCGF3 gene control, the test cancer patient is determined as an effective group.
  • the determination method of the level of expression is appropriately selected according to the measurement method and / or the comparison method.
  • the reagent of the present invention predicts the effect of cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent. As described later, it is divided into a reagent containing a primer or a probe or a reagent containing an antibody.
  • the use of the reagent of the present invention is for cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent. This is to determine the effect. That is, the reagent of the present invention is an effective group for cancer treatment in which the test patient uses a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent. It is used to determine whether there is a non-effective group. The effect can be determined by using the reagent of the present invention in the above-described screening method of the present invention.
  • the cancer type is a cancer type capable of performing cancer treatment using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • a taxane anticancer agent for example, but not limited to, stomach cancer, liver cancer, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, endometrial cancer, ovarian cancer, esophageal cancer, lung cancer, head and neck
  • examples include cancer, breast cancer, biliary tract cancer, bile duct cancer, and prostate cancer.
  • stomach cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, prostate cancer, and cervical cancer are preferable
  • stomach cancer, esophageal cancer, head and neck cancer, breast cancer, and lung cancer are more preferable
  • Gastric cancer is particularly preferred.
  • the cancer progression is preferably a cancer classified as a progression of stage II or higher, more preferably a cancer classified as a progression of stage III or higher, more preferably a classification of stage IV Cancer is mentioned.
  • the treatment method is a cancer treatment method using a combination of a taxane anticancer agent, a platinum complex anticancer agent, and a fluoropyrimidine anticancer agent.
  • taxane-based anticancer agents examples include docetaxel, paclitaxel (taxol), taxadiene, baccatin III, taxinin A, breviforiol, and taxapine D. Docetaxel or paclitaxel is preferable, and docetaxel is more preferable.
  • the dose of the taxane anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • platinum complex anticancer agent examples include cisplatin, carboplatin, nedaplatin, and oxaliplatin, with cisplatin being preferred.
  • the dose of the platinum complex anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • fluoropyrimidine anticancer agent examples include tegafur, fluorouracil, and flucytosine. Tegafur or fluorouracil is preferable, and tegafur is more preferable.
  • tegafur is used as the fluoropyrimidine anticancer agent, it is preferable to use gimeracil and oteracil potassium together, and the molar ratio of tegafur: gimeracil: oteracil potassium is, for example, 0.5-2: 0.
  • the dose of the fluorinated pyrimidine anticancer agent is, for example, 10 to 200 mg / m 2 , preferably 20 to 120 mg / m 2 , more preferably 40 to 100 mg / m 2 per day.
  • the unit “mg / m 2 ” indicates the dose per 1 m 2 of body surface area.
  • the treatment mode of the combined cancer treatment is particularly limited as long as it is a known method as a treatment mode of administering all of the fluoropyrimidine anticancer agent, the taxane anticancer agent, and the platinum complex anticancer agent.
  • a treatment schedule of about 1 to 4 weeks is set as one course, and this course is repeated a plurality of times.
  • the treatment schedule is such that the fluoropyrimidine anticancer agent is used for a certain period, preferably 7 to 28 days, more preferably 10 to 21 days, still more preferably 12 to After daily administration for 16 days, an anticancer agent non-administration period of a certain period, preferably 4 to 10 days, more preferably 6 to 8 days, is provided, and the middle of the administration period of the fluorinated pyrimidine anticancer agent (If the administration period is 14 days, preferably any one of the 5th to 11th days, preferably any one of the 7th to 9th days), the taxane anticancer agent and the platinum complex A schedule for administration of cancer drugs.
  • the reagent containing the primer or probe of the present invention specifically has a continuous base sequence having a length of at least 15 bases within the base sequence shown in any one of SEQ ID NOs: 1 to 15.
  • a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more that hybridizes (provided that, when the polynucleotide is RNA, the base “t” in the sequence is replaced with “u”) It is a reagent containing.
  • the probe or primer sequence contained in the reagent is a base of 15 bases or longer that specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15 There is no particular limitation as long as it consists of a polynucleotide having a sequence.
  • Such a polynucleotide has a length of at least 15 bases to a total base length of any of the base sequences shown in any one of SEQ ID NOs: 1 to 15, preferably 20 bases in the base sequence shown in any of SEQ ID NOs: 1 to 15.
  • a continuous base sequence of the entire base length of the base sequence represented by any one of SEQ ID NOs: 1 to 15, more preferably 30 base lengths to the entire base length of any of the base sequences represented by any of SEQ ID NOs: 1 to 15, Are designed as polynucleotides having a base length corresponding to the above.
  • Specific hybridization means that a specific hybrid is formed under a stringent hybridization condition and a non-specific hybrid is not formed.
  • Stringent hybridization conditions can be determined based on the melting temperature (Tm) of a nucleic acid that forms a hybrid according to a conventional method.
  • Tm melting temperature
  • the conditions are usually about “1 ⁇ SSC, 0.1% SDS, 37 ° C.”, more strictly “0.5 ⁇ SSC, 0.1% SDS, 42 ° C.” Strictly, “0.1 ⁇ SSC, 0.1% SDS, 65 ° C.” is the condition.
  • the polynucleotide preferably has a base sequence complementary to a continuous base sequence having a length of at least 15 bases of the base sequence shown in any one of SEQ ID NOs: 1 to 15, but the specific hybridization is performed as described above. If possible, they need not be completely complementary.
  • Such a polynucleotide is preferably 70% or more in base sequence as compared to a polynucleotide comprising a base sequence of at least 15 bases continuous in the base sequence shown in any of SEQ ID NOs: 1 to 15 or a complementary polynucleotide thereof.
  • the polynucleotide is preferably 80% or more, more preferably 90% or more, still more preferably 95% or more, particularly preferably 98% or more.
  • the identity of the base sequence can be calculated by identity search, sequence alignment program, BLAST, FASTA, ClustalW, or the like.
  • these polynucleotides can be prepared according to a conventional method using, for example, a commercially available nucleotide synthesizer based on the total base length of the base sequence represented by any of SEQ ID NOs: 1 to 15. It can also be prepared by PCR using the entire base length of the base sequence shown in any of SEQ ID NOs: 1 to 15 as a template.
  • a probe or primer contained in the reagent preferably, (I) a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more that specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in SEQ ID NO: 1 (hereinafter referred to as “ It may be expressed as “a probe or primer that recognizes SEQ ID NO: 1”), or (II) specifically hybridizes with a continuous base sequence of at least 15 bases in the base sequence shown in SEQ ID NO: 1 Specifically hybridize with a probe or primer comprising a polynucleotide having a base sequence of 15 bases or more in length and a continuous base sequence of at least 15 bases in the base sequence shown in any of SEQ ID NOs: 2 to 15.
  • a probe or primer contained in the reagent more preferably, (V) a probe or primer that recognizes SEQ ID NO: 1 and a probe or primer that recognizes SEQ ID NO: 2, or (VI) a probe or primer that recognizes SEQ ID NO: 1 and a probe or primer that recognizes SEQ ID NO: 2, and Examples include probes or primers that recognize any of SEQ ID NOs: 3 to 15.
  • a probe or primer contained in the reagent more preferably, (VII) a probe or primer that recognizes SEQ ID NO: 1, a probe or primer that recognizes SEQ ID NO: 2, and a probe or primer that recognizes SEQ ID NO: 3, or (VIII) a probe or primer that recognizes SEQ ID NO: 1, SEQ ID NO: And a probe or primer that recognizes SEQ ID NO: 3, and a probe or primer that recognizes any of SEQ ID NOs: 4 to 15.
  • a probe or primer contained in the reagent More preferably as a probe or primer contained in the reagent, (IX) a probe or primer that recognizes SEQ ID NO: 1, a probe or primer that recognizes SEQ ID NO: 2, a probe or primer that recognizes SEQ ID NO: 3, and a probe or primer that recognizes SEQ ID NO: 4, or (X) SEQ ID NO: A probe or primer that recognizes 1, a probe or primer that recognizes SEQ ID NO: 2, a probe or primer that recognizes SEQ ID NO: 3, a probe or primer that recognizes SEQ ID NO: 4, and any of SEQ ID NOs: 5 to 15 Or a probe or primer.
  • the probe or primer included in the reagent recognizes SEQ ID NO: 1, a probe or primer that recognizes SEQ ID NO: 2, a probe or primer that recognizes SEQ ID NO: 3, or recognizes SEQ ID NO: 4.
  • examples include a probe or primer, a probe or primer that recognizes SEQ ID NO: 5, a probe or primer that recognizes SEQ ID NO: 6, and a probe or primer that recognizes SEQ ID NO: 7.
  • the probe or primer included in the reagent is particularly preferably a probe or primer that recognizes SEQ ID NO: 1, a probe or primer that recognizes SEQ ID NO: 2, a probe or primer that recognizes SEQ ID NO: 3, or a probe that recognizes SEQ ID NO: 4.
  • a primer, a probe or primer that recognizes SEQ ID NO: 5 a probe or primer that recognizes SEQ ID NO: 6, a probe or primer that recognizes SEQ ID NO: 7, a probe or primer that recognizes SEQ ID NO: 8, or a probe that recognizes SEQ ID NO: 9
  • a primer, a probe or primer that recognizes SEQ ID NO: 10 a probe or primer that recognizes SEQ ID NO: 11, a probe or primer that recognizes SEQ ID NO: 12, a probe or primer that recognizes SEQ ID NO: 13, or a probe that recognizes SEQ ID NO: 14 Over Bed or primer, and a probe or primer and the like that recognize SEQ ID NO: 15.
  • the reagent containing the primer or probe of the present invention contains at least one primer or probe composed of the above-mentioned unlabeled or labeled polynucleotide.
  • primers or probes other reagents necessary for the measurement of gene expression products in the above-described screening method of the present invention, such as hybridization reagents and buffers, may be included as appropriate. .
  • the reagent containing the antibody of the present invention is a reagent containing an antibody that recognizes a polypeptide consisting of the amino acid sequence shown in any of SEQ ID NOs: 16 to 30.
  • the antibody used in the present invention is not limited as long as it can recognize and detect a polypeptide consisting of the amino acid sequence shown in any of SEQ ID NOs: 16 to 30, and may be any of a monoclonal antibody and a polyclonal antibody. Good. Specifically, “detectable” means that the presence of a protein can be detected by a known protein detection method, and preferably the presence of a protein can be detected by Western blotting or immunostaining.
  • the antibody may be an antibody prepared by using a polypeptide consisting of the amino acid sequence shown in any of SEQ ID NOs: 16 to 30 as an immunizing antigen, or consisting of the amino acid sequence shown in any of SEQ ID NOs: 16 to 30.
  • a polypeptide can be usually synthesized by a known method based on the amino acid sequence shown in any of SEQ ID NOs: 16 to 30 and the base sequence encoding it. For example, a chemical synthesis method using an amino acid synthesizer or a genetic engineering method can be used.
  • the antibody according to the present invention can be produced according to a conventional method (for example, Current protocol in Molecular Biology edit. Ausubel et al. (1987), Publish. John Wiley and Sons. Section 11.12-11.13).
  • a conventional method for example, Current protocol in Molecular Biology edit. Ausubel et al. (1987), Publish. John Wiley and Sons. Section 11.12-11.13.
  • an experimental animal is immunized, It can be obtained from the serum of the immunized animal according to a conventional method.
  • an experimental animal is immunized with the above-mentioned polynucleotide expressed and purified in Escherichia coli according to a conventional method, or with a polypeptide synthesized with these partial amino acid sequences according to a conventional method. Then, spleen cells obtained from the experimental animals and myeloma cells are fused to synthesize hybridoma cells, which can be obtained from the cells.
  • the antibody contained in the reagent is preferably (III) an antibody that recognizes a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 16 (hereinafter sometimes expressed as "an antibody that recognizes SEQ ID NO: 16") Or (IV) an antibody that recognizes a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 16, and Examples thereof include an antibody that recognizes a polypeptide consisting of the amino acid sequence shown in any of SEQ ID NOs: 17 to 30.
  • an antibody contained in the reagent more preferably, (XI) an antibody that recognizes SEQ ID NO: 16 and an antibody that recognizes SEQ ID NO: 17, or (XII) an antibody that recognizes SEQ ID NO: 16, and an antibody that recognizes SEQ ID NO: 17, and any one of SEQ ID NOs: 18 to 30 Antibody that recognizes.
  • an antibody contained in the reagent (XIII) an antibody that recognizes SEQ ID NO: 16, an antibody that recognizes SEQ ID NO: 17, and an antibody that recognizes SEQ ID NO: 18, or (XIV) an antibody that recognizes SEQ ID NO: 16, an antibody that recognizes SEQ ID NO: 17, and a sequence Examples thereof include an antibody recognizing number 18 and an antibody recognizing any of SEQ ID NOs: 19 to 30.
  • an antibody that recognizes SEQ ID NO: 16 an antibody that recognizes SEQ ID NO: 17, an antibody that recognizes SEQ ID NO: 18, and an antibody that recognizes SEQ ID NO: 19, or (XVI) an antibody that recognizes SEQ ID NO: 16, SEQ ID NO: An antibody recognizing SEQ ID NO: 18, an antibody recognizing SEQ ID NO: 19, and an antibody recognizing any of SEQ ID NOS: 20-30.
  • an antibody that recognizes SEQ ID NO: 16 an antibody that recognizes SEQ ID NO: 17, an antibody that recognizes SEQ ID NO: 18, an antibody that recognizes SEQ ID NO: 19, or a sequence that recognizes SEQ ID NO: 20
  • an antibody that recognizes SEQ ID NO: 21 an antibody that recognizes SEQ ID NO: 22.
  • an antibody that recognizes SEQ ID NO: 16 an antibody that recognizes SEQ ID NO: 17, an antibody that recognizes SEQ ID NO: 18, an antibody that recognizes SEQ ID NO: 19, or an antibody that recognizes SEQ ID NO: 20
  • the reagent containing the antibody of the present invention contains at least one of the above-mentioned unlabeled or labeled antibodies. Further, in addition to antibodies, other reagents necessary for the measurement of gene expression products in the above-described screening method of the present invention, such as antigen-antibody reaction reagents and buffers, may be included as appropriate.
  • Classification of effective group and ineffective group 20 patients with gastric cancer classified in stage III or stage IV are treated with 3 types of docetaxel, cisplatin, and tegafur as anticancer agents.
  • the effective group and the ineffective group were classified.
  • Table 2 shows the age, sex, and progression of cancer of patients who were treated.
  • Treatment is fluorinated pyrimidine anticancer drugs tegafur, gimeracil (prevents metabolization of tegafur other than fluorouracil), and oteracil potassium (fluorouracil reduces gastrointestinal toxicity)
  • the anticancer agent TS-1 (Takuma Pharmaceutical Co., Ltd.) (80 mg / m 2 ) containing a molar ratio of 1: 0.4: 1 is orally administered for 2 weeks, and the 8th day of the oral administration period
  • Intravenous administration of docetaxel 60 mg / m 2
  • cisplatin 60 mg / m 2
  • the treatment was carried out according to a treatment schedule of a total of 3 weeks, with a weekly non-cancer drug administration period.
  • the metastatic lesion was photographed by computed tomography (Computed Tomography), and the major axis of the metastatic tumor was measured.
  • the major axis of the metastasis measured before the treatment was compared with the major axis of the metastasis measured after the treatment, and the tumor reduction rate (the major axis of the metastasis after treatment / the major axis of the metastasis before treatment) was determined.
  • Microarray method (1) Perform upper gastrointestinal endoscopy before treatment, biopsy the gastric cancer tissue, and immediately store it frozen (2) Prepare a fresh frozen sliced section, and prepare a gastric cancer cell or cell by microdissection method Collect only normal gland ducts (3) Extract RNA from collected tissues according to conventional methods (4) Create cDNA from RNA using reverse transcriptase (5) Fragment cDNA and label with fluorescent dye Cy3 (6) Hybridization with a DNA chip loaded with 41,000 whole human genomes (7) Image images were created by scanning the DNA chip and quantified.
  • These 15 genes are PDGFB gene, PCGF3 gene, CISH gene, ANXA5 gene, ANTXR2 gene, B4GALT5 gene, PLK2 gene, ATP7B gene, FAM116A gene, HECA gene, JMJD2A gene, STYX gene, EGR1 gene, AVPI1 gene, and ERLIN1 gene.
  • Table 3 shows the microarray data for these 15 genes.
  • the numerical value indicates the gene expression level. From this result, it became clear that the expression level in the effective group tends to be higher than the expression level in the ineffective group for the PDGFB gene and the JMJD2A gene.
  • the expression level in the effective group is It became clear that the expression level tends to be lower than that in the ineffective group.
  • the genes whose protein expression levels were compared between the effective group and the non-effective group are PDGFB gene, CISH gene, ANTXR2 gene, PLK2 gene, EGR1 gene, ATP7B gene, and HECA gene.
  • Immunostaining was performed by the streptavidin-biotin-peroxidase method. That is, a thin slice of 2 ⁇ m was prepared from a formalin-fixed specimen of gastric cancer tissue, deparaffinized with alcohol, and then endogenous peroxidase was inactivated with 0.3% H 2 O 2. After immersing in 0.01 M citrate buffer for antigen activation treatment at 95 ° C. for 15 minutes, a primary antibody was added and reacted at 4 ° C. overnight.
  • the slide was thoroughly washed with phosphate buffer (PBS), reacted with a biotinylated secondary antibody, reacted with peroxidase / streptavidin, and then colored with Diaminobenzidine tetrahydrochloride (DAB).
  • PBS phosphate buffer
  • DAB Diaminobenzidine tetrahydrochloride
  • Effective group and ineffective group are determined by leave-one-out cross-validation method and N-fold method. Each patient in the patient group classified as “effective” or “ineffective” in the “classification” was predicted to be an effective group or an ineffective group.
  • N -192-19
  • the PDGFB gene, PCGF3 gene, CISH gene, or ANXA5 gene expression in the cell is knocked down using siRNA, and the fluoropyrimidine anticancer agent or taxane anticancer of the cell Changes in drug sensitivity to drugs were examined.
  • PCGF3 gene, CISH gene, or ANXA5 gene tends to be lower in the effective group than in the ineffective group. Therefore, by knocking down the PCGF3 gene, CISH gene, or ANXA5 gene in the cell, it is predicted that the cell will artificially become an effective group (group with high drug sensitivity).
  • siRNA sequences used are as shown in Table 5 below.
  • MKN45 cells were cultured in 96-well plates at 1.5 x 10 / well each, and transfection was performed by adding siPORT Amine 0.45 ⁇ l and siRNA 30 to 30 ⁇ M (/ 100 ⁇ l OptiMEM medium) as transfection reagents. It was. After culturing at 37 ° C and 5% CO2 for 6 hours, the culture solution was replaced with RPMI1640 with Fetal calf serum (FCS) added to a concentration of 10%, and 5-FU (TS-1 is in vivo And finally becomes 5-FU, which is the active form), and added with docetaxel, sputum or cisplatin, and further cultured for 48 hours, followed by MTT assay.
  • FCS Fetal calf serum
  • 5-FU (the final active substance of TS-1) has a final concentration of 0 ⁇ M, 7.8 ⁇ M, 15.6 ⁇ M, 31.3 ⁇ M, 62.5 ⁇ M, 125 ⁇ M, 250 ⁇ M, 500 ⁇ M, or 1000 ⁇ M, respectively.
  • Cisplatin is 0 ⁇ M, 0.0240 ⁇ M, 0.0980 ⁇ M, 0.390 ⁇ M, 1.560 ⁇ M, 250 ⁇ M, 250 ⁇ M, 1000 ⁇ M, 1000 ⁇ M, 0.61000 ⁇ M, or 0.61pM, 2.44pM, 9.77pM, 39.0pM It added so that it might become.
  • FIG. 2 shows the results of drugs changed by knockdown of each gene.
  • As control cells MKN45 cells supplemented with the same concentration of random siRNA were used.
  • FIG. 2 shows the drug concentration at 50% viability as IC50 with respect to cell viability when no drug is added.

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Abstract

La présente invention concerne : une méthode de sélection d'un groupe efficace de traitements anticancéreux combinant l'utilisation de trois agents, à savoir un agent anticancéreux à base de taxane, un agent anticancéreux à base d'un complexe de platine et un agent anticancéreux à base de fluorure de pyrimidine ; et un réactif pour prédire l'efficacité d'un traitement anticancéreux combinant l'utilisation des trois agents précédemment mentionnés. La méthode de sélection de l'invention utilise comme indicateur la quantité du produit d'expression d'au moins un gène choisi dans le groupe comprenant PDGFB, PCGF3, CISH, ANXA5, ANTXR2, B4GALT5, PLK2, ATP7B, AM116A, HECA, JMJD2A, STYX, EGR1, AVPI1 et ERLIN1.
PCT/JP2012/055948 2011-03-08 2012-03-08 Méthode de sélection d'un groupe efficace de traitements anticancéreux combinant l'utilisation de trois agents, à savoir un agent anticancéreux à base de taxane, un agent anticancéreux à base d'un complexe de platine et un agent anticancéreux à base de fluorure de pyrimidine WO2012121324A1 (fr)

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
CN103150467A (zh) * 2013-02-05 2013-06-12 上海交通大学 一种通过基因组表达谱检测药物不良反应的方法
US11077208B2 (en) 2015-12-18 2021-08-03 Ucl Business Ltd Wilson's disease gene therapy

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JP2009050189A (ja) * 2007-08-24 2009-03-12 Sumitomo Bakelite Co Ltd 抗癌剤の有効性予測方法

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103150467A (zh) * 2013-02-05 2013-06-12 上海交通大学 一种通过基因组表达谱检测药物不良反应的方法
US11077208B2 (en) 2015-12-18 2021-08-03 Ucl Business Ltd Wilson's disease gene therapy

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