ES2727103T8 - Conjugado anticuerpo-fármaco para IGF-1R y su utilización para el tratamiento del cáncer - Google Patents
Conjugado anticuerpo-fármaco para IGF-1R y su utilización para el tratamiento del cáncerInfo
- Publication number
- ES2727103T8 ES2727103T8 ES15720045T ES15720045T ES2727103T8 ES 2727103 T8 ES2727103 T8 ES 2727103T8 ES 15720045 T ES15720045 T ES 15720045T ES 15720045 T ES15720045 T ES 15720045T ES 2727103 T8 ES2727103 T8 ES 2727103T8
- Authority
- ES
- Spain
- Prior art keywords
- igf
- antibody
- drug conjugate
- cancer treatment
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14305620 | 2014-04-25 | ||
| PCT/EP2015/059045 WO2015162291A1 (en) | 2014-04-25 | 2015-04-27 | Igf-1r antibody-drug-conjugate and its use for the treatment of cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2727103T3 ES2727103T3 (es) | 2019-10-14 |
| ES2727103T8 true ES2727103T8 (es) | 2020-03-02 |
Family
ID=50630736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15720045T Active ES2727103T3 (es) | 2014-04-25 | 2015-04-27 | Conjugado anticuerpo-fármaco para IGF-1R y su utilización para el tratamiento del cáncer |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US10633448B2 (es) |
| EP (2) | EP3498301A1 (es) |
| JP (1) | JP6258523B2 (es) |
| KR (1) | KR101795984B1 (es) |
| CN (1) | CN106456800B (es) |
| AU (1) | AU2015250759B2 (es) |
| BR (1) | BR112016024619A2 (es) |
| CA (1) | CA2946469C (es) |
| CY (1) | CY1121783T1 (es) |
| DK (1) | DK3134124T3 (es) |
| ES (1) | ES2727103T3 (es) |
| HR (1) | HRP20190888T8 (es) |
| HU (1) | HUE044862T2 (es) |
| IL (1) | IL248455B (es) |
| LT (1) | LT3134124T (es) |
| MA (2) | MA47811A (es) |
| MX (1) | MX2016013704A (es) |
| MY (1) | MY186711A (es) |
| PL (1) | PL3134124T3 (es) |
| PT (1) | PT3134124T (es) |
| RS (1) | RS58742B1 (es) |
| RU (1) | RU2692563C2 (es) |
| SA (1) | SA516380120B1 (es) |
| SI (1) | SI3134124T1 (es) |
| TN (1) | TN2016000472A1 (es) |
| UA (1) | UA120364C2 (es) |
| WO (1) | WO2015162291A1 (es) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3134124T3 (pl) * | 2014-04-25 | 2019-09-30 | Pierre Fabre Medicament | Koniugat przeciwciało IGF-IR-lek i jego zastosowanie do leczenia raka |
| MX2018005070A (es) | 2015-10-26 | 2018-09-06 | Pf Medicament | Composición para el tratamiento de cáncer con expresión del igf-1r. |
| WO2017153432A1 (en) | 2016-03-07 | 2017-09-14 | Pierre Fabre Medicament | A new universal method to capture and analyze adcs for characterization of drug distribution and the drug-to-antibody ratio in biological samples |
| CA3113378C (en) | 2018-09-27 | 2024-01-02 | Pierre Fabre Medicament | Sulfomaleimide-based linkers and corresponding conjugates |
| CN111327570B (zh) | 2018-12-14 | 2021-09-17 | 北京京东尚科信息技术有限公司 | 验证方法、装置和计算机可读存储介质 |
| EP3735991A1 (fr) | 2019-05-06 | 2020-11-11 | Pierre Fabre Medicament | Adc pour un traitement concomitant ou postérieur au docétaxel |
| EP3909612A1 (en) | 2020-05-12 | 2021-11-17 | Life Science Inkubator Betriebs GmbH & Co. KG | Composition of nanoparticles |
| WO2023240223A2 (en) * | 2022-06-10 | 2023-12-14 | Acelyrin, Inc. | Anti-igf-1r antibody compositions |
| EP4353220A1 (en) | 2022-10-12 | 2024-04-17 | Pierre Fabre Medicament | Use of a liquid aqueous composition for solubilization and stabilization of an antibody-drug conjugate |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB9014932D0 (en) | 1990-07-05 | 1990-08-22 | Celltech Ltd | Recombinant dna product and method |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| JPH05244982A (ja) | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化ｂ−ｂ１０ |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| ATE282630T1 (de) | 1993-10-01 | 2004-12-15 | Teikoku Hormone Mfg Co Ltd | Dolastatin-derivate |
| US7241444B2 (en) | 2002-01-18 | 2007-07-10 | Pierre Fabre Medicament | Anti-IGF-IR antibodies and uses thereof |
| BRPI0510883B8 (pt) * | 2004-06-01 | 2021-05-25 | Genentech Inc | composto conjugado de droga e anticorpo, composição farmacêutica, método de fabricação de composto conjugado de droga e anticorpo e usos de uma formulação, de um conjugado de droga e anticorpo e um agente quimioterapêutico e de uma combinação |
| KR101270829B1 (ko) | 2004-09-23 | 2013-06-07 | 제넨테크, 인크. | 시스테인 유전자조작 항체 및 접합체 |
| EA016577B1 (ru) | 2005-09-26 | 2012-06-29 | Медарекс, Инк. | Конъюгаты антитело-лекарство и их применение |
| AR064464A1 (es) | 2006-12-22 | 2009-04-01 | Genentech Inc | Anticuerpos anti - receptor del factor de crecimiento insulinico |
| AR065803A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Uso de un polipeptido de il- 18 humana y un anticuerpo anti- cd para preparar unmedicamento |
| JP5290276B2 (ja) | 2007-05-08 | 2013-09-18 | ジェネンテック， インコーポレイテッド | システイン改変抗ｍｕｃ１６抗体および抗体−薬物結合体 |
| MX2010003718A (es) | 2007-10-19 | 2010-04-21 | Genentech Inc | Anticuerpos anti-tenb2 producidos por ingenieria de cisteina y conjugados de farmaco y anticuerpo. |
| MY159553A (en) | 2008-04-11 | 2017-01-13 | Seattle Genetics Inc | Detection and treatment of pancreatic, ovarian and other cancers |
| CA2754531A1 (en) | 2009-03-06 | 2010-09-30 | Seattle Genetics, Inc. | Antibody drug conjugates (adc) that bind to 24p4c12 proteins |
| WO2010146059A2 (en) * | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| US20130028917A1 (en) | 2010-04-15 | 2013-01-31 | Spirogen Developments Sàrl | Pyrrolobenzodiazepines and conjugates thereof |
| ES2528956T3 (es) | 2010-06-10 | 2015-02-13 | Seattle Genetics, Inc. | Nuevos derivados de auristatina y su uso |
| CN103379912B (zh) | 2010-09-29 | 2016-03-16 | 西雅图基因公司 | 正羧烷基耳他汀及其应用 |
| CN103561759B (zh) * | 2010-10-22 | 2016-10-12 | 西雅图遗传学公司 | 以奥里斯他汀(AURISTATIN)为主的抗体药物结合物与PI3K-AKT mTOR路径抑制剂之间的协同作用 |
| US9676871B2 (en) | 2010-11-05 | 2017-06-13 | Pfizer Inc. | Engineered polypeptide conjugates and methods for making thereof using transglutaminase |
| JP6023097B2 (ja) | 2011-03-16 | 2016-11-09 | シアトル ジェネティックス， インコーポレイテッド | Ｎカルボキシアルキルオーリスタチンおよびその使用 |
| US9150644B2 (en) * | 2011-04-12 | 2015-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II |
| MX359217B (es) | 2011-05-27 | 2018-09-19 | Ambrx Inc | Composiciones que contienen, métodos que involucran, y usos de derivados de dolastatina unidos a aminoácidos no naturales. |
| EP2714685B1 (en) | 2011-05-27 | 2016-10-19 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acid linked dolastatin derivatives |
| US8815226B2 (en) | 2011-06-10 | 2014-08-26 | Mersana Therapeutics, Inc. | Protein-polymer-drug conjugates |
| SG11201408153YA (en) | 2012-06-07 | 2015-01-29 | Ambrx Inc | Prostate-specific membrane antigen antibody drug conjugates |
| ES2712648T3 (es) | 2012-06-19 | 2019-05-14 | Ambrx Inc | Conjugados de fármaco de anticuerpo anti-CD70 |
| US20140017265A1 (en) | 2012-07-05 | 2014-01-16 | Mersana Therapeutics, Inc. | Terminally Modified Polymers and Conjugates Thereof |
| WO2014026286A1 (en) | 2012-08-14 | 2014-02-20 | Angiochem Inc. | Conjugates including an antibody moiety, a polypeptide that traverses the blood-brain barrier, and a cytotoxin |
| WO2014096551A1 (en) | 2012-12-21 | 2014-06-26 | Glykos Finland Oy | Linker-payload molecule conjugates |
| FR3005051A1 (fr) | 2013-04-25 | 2014-10-31 | Pf Medicament | Derives de la dolastatine 10 et d'auristatines |
| CA2946796C (en) * | 2014-04-25 | 2019-10-22 | Pierre Fabre Medicament | Antibody-drug-conjugate and its use for the treatment of cancer |
| PL3134124T3 (pl) * | 2014-04-25 | 2019-09-30 | Pierre Fabre Medicament | Koniugat przeciwciało IGF-IR-lek i jego zastosowanie do leczenia raka |
| EP3783033A1 (en) * | 2014-04-25 | 2021-02-24 | Pierre Fabre Medicament | Igf-1r antibody and its use as addressing vehicle for the treatment of cancer |
| MX2018005070A (es) * | 2015-10-26 | 2018-09-06 | Pf Medicament | Composición para el tratamiento de cáncer con expresión del igf-1r. |
-
2015
- 2015-04-27 PL PL15720045T patent/PL3134124T3/pl unknown
- 2015-04-27 EP EP19154902.1A patent/EP3498301A1/en not_active Withdrawn
- 2015-04-27 CN CN201580033382.0A patent/CN106456800B/zh active Active
- 2015-04-27 LT LTEP15720045.2T patent/LT3134124T/lt unknown
- 2015-04-27 SI SI201530751T patent/SI3134124T1/sl unknown
- 2015-04-27 RU RU2016145444A patent/RU2692563C2/ru active
- 2015-04-27 BR BR112016024619A patent/BR112016024619A2/pt not_active Application Discontinuation
- 2015-04-27 PT PT15720045T patent/PT3134124T/pt unknown
- 2015-04-27 MX MX2016013704A patent/MX2016013704A/es active IP Right Grant
- 2015-04-27 CA CA2946469A patent/CA2946469C/en active Active
- 2015-04-27 TN TN2016000472A patent/TN2016000472A1/en unknown
- 2015-04-27 UA UAA201611833A patent/UA120364C2/uk unknown
- 2015-04-27 US US15/306,351 patent/US10633448B2/en active Active
- 2015-04-27 KR KR1020167031683A patent/KR101795984B1/ko active IP Right Grant
- 2015-04-27 HU HUE15720045 patent/HUE044862T2/hu unknown
- 2015-04-27 DK DK15720045.2T patent/DK3134124T3/da active
- 2015-04-27 MA MA047811A patent/MA47811A/fr unknown
- 2015-04-27 ES ES15720045T patent/ES2727103T3/es active Active
- 2015-04-27 WO PCT/EP2015/059045 patent/WO2015162291A1/en active Application Filing
- 2015-04-27 RS RS20190615A patent/RS58742B1/sr unknown
- 2015-04-27 MY MYPI2016703874A patent/MY186711A/en unknown
- 2015-04-27 EP EP15720045.2A patent/EP3134124B1/en active Active
- 2015-04-27 JP JP2016564149A patent/JP6258523B2/ja active Active
- 2015-04-27 AU AU2015250759A patent/AU2015250759B2/en not_active Ceased
- 2015-04-27 MA MA39909A patent/MA39909B1/fr unknown
-
2016
- 2016-10-23 IL IL248455A patent/IL248455B/en active IP Right Grant
- 2016-10-23 SA SA516380120A patent/SA516380120B1/ar unknown
-
2019
- 2019-05-15 CY CY20191100523T patent/CY1121783T1/el unknown
- 2019-05-15 HR HRP20190888TT patent/HRP20190888T8/hr unknown
-
2020
- 2020-02-26 US US16/801,491 patent/US11661457B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2764110T8 (es) | Conjugado anticuerpo-fármaco y su utilización para el tratamiento del cáncer | |
| HRP20180876T1 (hr) | Adc duokarmicina, namijenjeni upotrebi u liječenju raka mokraćnog mjehura | |
| BR112017011771A2 (pt) | métodos e composições para o tratamento de câncer | |
| BR112017008399A2 (pt) | abordagem de imunoterapia de combinação para tratamento de câncer | |
| ES2727103T8 (es) | Conjugado anticuerpo-fármaco para IGF-1R y su utilización para el tratamiento del cáncer | |
| PT3204018T (pt) | Uso neoadjuvante de conjugados anticorpo-fármaco | |
| IL251630A0 (en) | Combined therapy for use in cancer treatment | |
| BR112016027041A2 (pt) | Combinações farmacêuticas para tratamento do câncer | |
| BR112015028115A2 (pt) | métodos e composições para o tratamento de câncer | |
| IL276733A (en) | Use of Aribolin in cancer treatment | |
| CL2016000770A1 (es) | Anticuerpos conjugados contra ly75 para el tratamiento del cáncer | |
| GB201420533D0 (en) | Use of Nanomaterials in treating cancer | |
| GB201409363D0 (en) | Skin cancer treatment | |
| DK3302478T3 (da) | Pac-1 kombinations behandling | |
| DK3407909T3 (da) | Cancerbehandling | |
| TH1601003807A (th) | คอนจูเกตของแอนติ-trop2 แอนติบอดี-ยา | |
| TH1501004170A (th) | องค์ประกอบอนุภาคนาโนอนินทรีย์ร่วมกับรังสีไอออไนซ์สำหรับการรักษามะเร็ง | |
| DK3092039T3 (da) | Hudcancerbehandling med strålingsterapi | |
| TH1501006324A (th) | การบำบัดมะเร็งด้วยไดไฮโดรพิแรซิโน-พิแรซีน | |
| TH1501007058A (th) | อนุพันธ์ไพราโซโลไพร์โรลิดีน และการใช้งานของพวกมันในการบำบัดโรค | |
| GB201410695D0 (en) | Uses of oligouronates in cancer treatment | |
| GB201411111D0 (en) | bis-Pyridazine compounds and their use in treating cancer | |
| ZA201403006B (en) | Composition for use in treatment of cancer |