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EGFR Mutations in Non-Small Cell Lung Cancer

非小细胞肺癌中的 EGFR 突变

基本信息

批准号：
8507610
负责人：
BRUCE E. JOHNSON
金额：
$ 46.56万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8507610
关键词：
Accounting Agonist Asia Biological Biological Markers Cancer Patient Cancer cell line Cell Line Cell model China Clinical Clinical Research Combination Drug Therapy Deletion Mutation Development Drug resistance Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Europe European Exons Far East Frequencies Gatekeeping Gefitinib Gene Mutation Genomics Grant Harvest Hepatocyte Growth Factor In Vitro Japan Malignant neoplasm of lung Monitor Monoclonal Antibodies Mutation Non-Small-Cell Lung Carcinoma Outcome Pathogenesis Patients Pharmaceutical Preparations Phase III Clinical Trials Platinum Progression-Free Survivals Property Prospective Studies Publishing Randomized Research Resistance Resistance development Retrospective Studies Signal Transduction Somatic Mutation Systemic Therapy Therapeutic Time Toxic effect Tumor Cell Line Tumor-Derived Tyrosine Kinase Inhibitor United States Work base chemotherapy clinical efficacy improved in vivo Model inhibitor/antagonist insight kinase inhibitor member mutant novel phase 2 study preclinical study prospective research study resistance mechanism resistance mutation response therapy development trend tumor

项目摘要

DESCRIPTION (provided by applicant): Non-small cell lung (NSCLC) cancer is responsible for approximately 85% of the 221,130 lung cancer cases in the US in 2011. Chemotherapy and chemotherapy with targeted monoclonal antibodies for patients with NSCLC remain modestly effective. Therefore, more effective targeted agents are needed for systemic therapy of different NSCLCs as well as the biomarkers associated with treatment benefit. The association between somatic mutations in the epidermal growth factor receptor (EGFR) and the clinical efficacy of the EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, was discovered in 2004. Subsequent clinical studies done in Japan, China, East Asia, and Europe showed NSCLC patients with EGFR mutations treated with gefitinib or erlotinib have a 2-3 fold greater response and progression-free survival with less toxicity than those treated with platinum-based systemic chemotherapy. Further information is needed about patients with NSCLC and EGFR mutations treated with the different EGFR inhibitors in the US, Europe, and around the world. In addition, defining the mechanisms of resistance, identifying means of overcoming resistance to EGFR inhibitors, and improvements in the inhibitors are needed. The aims of the study are to prospectively validate the frequency and type of acquired resistance mutations and genomic changes arising in subjects with advanced NSCLC and somatic sensitizing mutations of EGFR treated with EGFR inhibitors. Studies of EGFR mutations in NSCLC patients treated with EGFR inhibitors around the world will define the relationship between EGFR mutations, response to treatment, progression-free survival, and survival in subjects with NSCLC treated with erlotinib and gefitinib in subjects with European ethnic background and those from East Asia. The experiments on different therapeutic approaches in lung cancer cell lines and models of acquired resistance to EGFR inhibitors will be done by studying tumors and tumor cell lines harvested or established from patients with clinical resistance to EGFR tyrosine kinase inhibitors. This will facilitate the development of more effective EGFR inhibitors either alone, or with other tyrosine kinase inhibitors and additional targeted agents.

描述（由申请人提供）：2011年，非小细胞肺癌（NSCLC）占美国221，130例肺癌病例的约85%。化疗和靶向单克隆抗体化疗对NSCLC患者仍有一定的疗效。因此，需要更有效的靶向药物用于不同NSCLC的全身治疗以及与治疗益处相关的生物标志物。2004年发现表皮生长因子受体（EGFR）的体细胞突变与EGFR酪氨酸激酶抑制剂吉非替尼和厄洛替尼的临床疗效之间存在关联。随后在日本、中国、东亚和欧洲进行的临床研究显示，与接受铂类全身化疗的患者相比，接受吉非替尼或厄洛替尼治疗的EGFR突变NSCLC患者的缓解率和无进展生存期高2-3倍，毒性更低。需要更多关于美国、欧洲和世界各地接受不同EGFR抑制剂治疗的NSCLC和EGFR突变患者的信息。此外，还需要确定耐药机制，确定克服EGFR抑制剂耐药的方法，以及改善抑制剂。本研究的目的是前瞻性验证接受EGFR抑制剂治疗的晚期NSCLC和EGFR体细胞致敏突变受试者中出现的获得性耐药突变和基因组变化的频率和类型。在全球范围内对接受EGFR抑制剂治疗的NSCLC患者进行的EGFR突变研究将确定EGFR突变、治疗应答、无进展生存期以及欧洲种族背景受试者和东亚受试者接受厄洛替尼和吉非替尼治疗的NSCLC受试者的生存期之间的关系。将通过研究从EGFR酪氨酸激酶抑制剂临床耐药患者中收获或建立的肿瘤和肿瘤细胞系，在肺癌细胞系和EGFR抑制剂获得性耐药模型中进行不同治疗方法的实验。这将促进更有效的EGFR抑制剂的开发，无论是单独的，还是单独的。与其他酪氨酸激酶抑制剂和其他靶向药物联用。