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：
8852562
负责人：
BRUCE E. JOHNSON
金额：
$ 49.53万
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 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8852562
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 DNA Sequence Alteration 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 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 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 phase III trial 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）：非小细胞肺（NSCLC）癌症在2011年美国造成221,130例肺癌病例中约85％。针对NSCLC患者的靶向单克隆抗体化疗和化学疗法仍然适度有效。因此，需要更有效的靶向剂来对不同的NSCLC以及与治疗益处相关的生物标志物进行全身治疗。 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与基于铂的全身化疗治疗的无毒性相比，无进展生存率具有较低的毒性。需要有关在美国，欧洲和世界各地使用不同EGFR抑制剂治疗的NSCLC和EGFR突变患者的进一步信息。此外，需要定义抗药性机制，确定克服对EGFR抑制剂的抗性的手段以及抑制剂的改善。该研究的目的是前瞻性地验证在晚期NSCLC和用EGFR抑制剂治疗的EGFR的受试者中产生的获得性抗性突变和基因组变化的频率和类型。在世界各地用EGFR抑制剂治疗的NSCLC患者中的EGFR突变的研究将定义EGFR突变，对治疗的反应，无进展的无进展生存期以及在欧洲民族背景和来自东亚的受试者中用Erlotinib和Gefitinib治疗的NSCLC受试者的生存之间的关系。在肺癌细胞系中不同治疗方法的实验以及对EGFR抑制剂的耐药性模型的实验，可以通过研究从具有临床对EGFR酪氨酸激酶抑制剂的临床耐药性的患者中收获或确定的肿瘤和肿瘤细胞系。这将促进更有效的EGFR抑制剂的开发，或者与其他酪氨酸激酶抑制剂和其他靶向剂。