JP6149034B2 - 上皮成長因子受容体遺伝子における変異 - Google Patents
上皮成長因子受容体遺伝子における変異 Download PDFInfo
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Description
ccaaaattataXYZaacagaggtga(I)
(式中、ヌクレオチドXYZは、AGA、AGG、CGT、CGC、CGAおよびCGGからなる群から選択されるヌクレオチドの組み合わせである)
に定義される一般的配列により概略的に表すことができる。
野生型プローブ(標識された配列番号6):
VIC−5’−CACCTCTGTTGCTTATAA−3’−MGB
変異特異的プローブ(標識された配列番号5):
FAM−5’−CACCTCTGTTTCTTATAATT−3’−MGB
腫瘍被検査物はmCRC患者の診断の間に、または外科手術から得た。生検は最も入手しやすい悪性病変(原発性腫瘍または転移のいずれか)から得た。
セツキシマブ(アービタックス)およびパニツムマブ(ベクチビックス)はHospital del Mar’s Pharmacyから得、両方のモノクローナル抗体はすぐに使えた。ゲフィチニブはSelleck Chemicals(Houston、TX、USA)から得、DMSOに溶解し、アリコートし、−20℃で保存した。精製したEGF組換えタンパク質はCalbiochem(San Diego、CA、USA)から購入し、PBS0,1%BSAに溶解し、アリコートし、−20℃で保存した。
本発明のS492R EGFR変異がセツキシマブに対する観測された抵抗性の原因であったかどうかを確立するために、完全長の野生型EGFRおよびS492R EGFR変異を、検出可能な内因性EGFR発現を欠いている培養したNIH3T3マウス胎児線維芽細胞株において異所的に発現させた。
セツキシマブに対する獲得抵抗の機構としてのこの変異の臨床的関連を評価するために、S492R EGFR変異が、セツキシマブに対する初期応答後に疾患進行を経験している転移性結腸直腸癌を患っている患者において見出され得るかどうかを試験した。
Mendelsohn J, Baselga J et al., "Epidermal growth factor receptor targeting in cancer". Semin Oncol - 2006, Vol. 33, pp.: 369-38
Goncalves et al., “A polymorphism of the EGFR extracellular domain is associated with progression free-survival in metastasic colorectal cancer pateints receiving cetuximab-based treatment”, BMC Cancer 2008, Vol 8:169.
Eisenhauer et al., “New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)”, Eur J Cancer 2009, Vol. 45(2):228-247.
De Roock et al., “Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastasic colorectal cancer: a retrospective consortium analysis”, Lancet Oncol - 2010, Vol. 11, pp.:753-762
Loupakis et al., “PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit of cetuximab plus irinotecan for patients with metastasic colorectal cancer”, J Clin Oncol - 2009, Vol. 27, pp.:2622-2629.
Karapetis et al., "K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer", The New England Journal of Medicine - 2008, Vol. 359, pp.: 1757-1765.
Montagut et al., “Mitogen-activated protein kinase phosphatase-1 (MKP-1) impairs the response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab in metastasic colorectal cancer patients”, Br. J Cancer - 2010, Vol. 102, pp.: 1137-1144.
Amado et al., “Wild-type KRAS is required for panitumumab efficacy in patients with metastasic colorectal cancer”, J. Clin Oncol - 2008, Vol. 28, pp.: 1626-1634
Pao et al., “Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain”, PloS Med 2005; 2:e73
Lynch TJ et al., "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib", N Engl J Med-2004, Vol. 350, pp:2129-2139.
Paez JG et al., "EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy", Science-2004, Vol. 304, pp.:1497-500.
Pao W et al., "EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib", Proc Natl Acad Sci U S A-2004, Vol. 101, pp.:13306-13311
Claims (15)
- 配列番号1(TKIIRNRGE)の配列からなるペプチド。
- 配列番号1をコードする配列からなるオリゴヌクレオチド。
- 配列番号2、配列番号13、配列番号14、配列番号15、配列番号16および配列番号17からなる群から選択される核酸配列からなる、請求項2に記載のオリゴヌクレオチド。
- 配列番号3(gggacctccggtcagaaaa)および4(cggtgacttactgcagctgttt)からなるプライマーのセット。
- 配列番号5(cacctctgtttcttataatt)からなるオリゴヌクレオチド。
- 配列番号6(cacctctgttgcttataa)からなるオリゴヌクレオチド。
- 請求項5に記載のオリゴヌクレオチドを含むキット。
- 請求項6に記載のオリゴヌクレオチドをさらに含む、請求項7に記載のキット。
- 請求項4に記載のプライマーのセットをさらに含む、請求項7または8に記載のキット。
- KRASおよび/またはPIK3CAおよび/またはBRAF遺伝子における変異を検出するための試薬をさらに含む、請求項7から9のいずれか一項に記載のキット。
- セツキシマブおよび/またはパニツムマブを含む治療レジメンに対する対象の応答の予測に使用するための、請求項7から10のいずれか一項に記載のキット。
- 対象が癌に罹患している、請求項11に記載の使用のためのキット。
- 癌が、転移性結腸直腸癌および頭頸部癌からなる群から選択される、請求項12に記載の使用のためのキット。
- 対象から得た試料中の配列番号8に対応するアミノ酸配列の492位におけるアルギニンの存在または非存在を識別するインビトロ方法であって、遺伝子型法、および/またはタンパク質シークエンシング法からなる群から選択される手段によって配列番号8の492位におけるアミノ酸を決定することを含む、方法。
- セツキシマブおよび/またはパニツムマブを含む治療レジメンに対する、対象の応答を予測するインビトロ方法であって、i)請求項14の方法に記載の、対象から得た試料中の配列番号8に対応するアミノ酸配列の492位におけるアルギニンの存在または非存在を決定する工程と、ii)工程i)において識別されたアルギニンの存在を、セツキシマブを含む治療レジメンに対する対象の抵抗性と関連付ける工程、または工程i)において識別されたアルギニンの非存在を、パニツムマブを含む治療レジメンに対する対象の応答と関連付ける工程とを含む、方法。
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EP11382270A EP2554551A1 (en) | 2011-08-03 | 2011-08-03 | Mutations in the epidermal growth factor receptor gene |
EP11382270.4 | 2011-08-03 | ||
PCT/EP2012/065090 WO2013017645A1 (en) | 2011-08-03 | 2012-08-02 | Mutations in the epidermal growth factor receptor gene |
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US (1) | US9765399B2 (ja) |
EP (3) | EP2554551A1 (ja) |
JP (1) | JP6149034B2 (ja) |
KR (1) | KR20140072035A (ja) |
CN (1) | CN103717616B (ja) |
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BR (1) | BR112014002373A2 (ja) |
CA (1) | CA2842270C (ja) |
ES (1) | ES2556468T3 (ja) |
IN (1) | IN2014CN00570A (ja) |
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Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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US8691231B2 (en) | 2011-06-03 | 2014-04-08 | Merrimack Pharmaceuticals, Inc. | Methods of treatment of tumors expressing predominantly high affinity EGFR ligands or tumors expressing predominantly low affinity EGFR ligands with monoclonal and oligoclonal anti-EGFR antibodies |
WO2015175705A1 (en) | 2014-05-13 | 2015-11-19 | Board Of Regents, The University Of Texas System | Gene mutations and copy number alterations of egfr, kras and met |
MA39599A (fr) | 2014-05-14 | 2016-10-05 | Merrimack Pharmaceuticals Inc | Dosage et administration d'agents thérapeutiques anti-egfr |
CN106573967B (zh) * | 2014-07-28 | 2022-02-18 | 玛尔医学研究所基金会 | 表皮生长因子受体基因的胞外域iii中的突变 |
CN104531854B (zh) * | 2014-11-10 | 2017-01-18 | 中国人民解放军第三〇七医院 | 检测西妥昔单抗治疗转移性结直肠癌耐药的试剂盒 |
CA2983890A1 (en) * | 2015-04-24 | 2016-10-27 | Merrimack Pharmaceuticals, Inc. | Methods of treating patients having mutations in the extracellular domain of epidermal growth factor receptor (egfr) with a combination of three fully human monoclonal anti-egfr antibodies |
RU2626682C1 (ru) * | 2016-07-20 | 2017-07-31 | Федеральное государственное бюджетное учреждение "Ростовский научно-исследовательский онкологический институт" Министерства здравоохранения Российской Федерации | Способ прогнозирования резистентности опухоли к таргетной терапии цетуксимабом у больных плоскоклеточным раком языка и слизистой дна полости рта |
CN111499749B (zh) * | 2020-03-13 | 2021-11-09 | 浙江大学 | 一种西妥昔单抗突变体及应用 |
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CA2558753A1 (en) | 2004-03-01 | 2005-09-15 | University Of Chicago | Polymorphisms in the epidermal growth factor receptor gene promoter |
TW200533339A (en) | 2004-03-16 | 2005-10-16 | Bristol Myers Squibb Co | Therapeutic synergy of anti-cancer compounds |
WO2006009694A2 (en) * | 2004-06-14 | 2006-01-26 | Imclone Sysetms Incorporated | Crystal of egfr extracellular domain and cetuximab fab fragment and uses thereof |
WO2006091899A2 (en) * | 2005-02-24 | 2006-08-31 | Amgen Inc. | Epidermal growth factor receptor mutations |
CN1737162A (zh) * | 2005-03-16 | 2006-02-22 | 南京中医药大学附属医院(江苏省中医院) | 表皮生长因子受体(egfr)基因测序检测方法 |
US7981606B2 (en) * | 2005-12-21 | 2011-07-19 | Roche Molecular Systems, Inc. | Control for nucleic acid testing |
US8680041B2 (en) * | 2006-10-26 | 2014-03-25 | Genentech, Inc. | Genetic variations associated with tumors |
AU2008205456A1 (en) | 2007-01-18 | 2008-07-24 | University Of Southern California | Polymorphisms in the EGFR pathway as markers for cancer treatment |
ES2609094T3 (es) * | 2007-01-25 | 2017-04-18 | Dana-Farber Cancer Institute, Inc. | Uso de anticuerpos anti-EGFR en el tratamiento de enfermedades mediadas por un EGFR mutante |
US8137919B2 (en) * | 2008-04-10 | 2012-03-20 | Montefiore Medical Center | Method of determining the sensitivity of cancer cells to EGFR inhibitors including cetuximab, panitumumab and erlotinib |
EP3216874A1 (en) * | 2008-09-05 | 2017-09-13 | TOMA Biosciences, Inc. | Methods for stratifying and annotating cancer drug treatment options |
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CN103717616A (zh) | 2014-04-09 |
EP2739648A1 (en) | 2014-06-11 |
RU2014107908A (ru) | 2015-09-10 |
US20140170662A1 (en) | 2014-06-19 |
CN103717616B (zh) | 2016-06-29 |
EP2554551A1 (en) | 2013-02-06 |
US9765399B2 (en) | 2017-09-19 |
EP2995623A1 (en) | 2016-03-16 |
KR20140072035A (ko) | 2014-06-12 |
ES2556468T3 (es) | 2016-01-18 |
CA2842270A1 (en) | 2013-02-07 |
CA2842270C (en) | 2019-10-29 |
IN2014CN00570A (ja) | 2015-04-03 |
WO2013017645A1 (en) | 2013-02-07 |
JP2014521342A (ja) | 2014-08-28 |
EP2739648B1 (en) | 2015-09-16 |
AU2012292024A1 (en) | 2014-02-27 |
BR112014002373A2 (pt) | 2017-02-21 |
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