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）： 2011 年美国 221,130 例肺癌病例中约 85% 为非小细胞肺癌 (NSCLC)。化疗和靶向单克隆抗体化疗对 NSCLC 患者仍然有效。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获益相关的生物标志物。表皮生长因子受体 (EGFR) 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的关联于 2004 年被发现。随后在日本、中国、东亚和欧洲进行的临床研究表明，非小细胞肺癌 (NSCLC)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 突变患者的反应和无进展生存期高出 2-3 倍，且毒性更小。需要有关美国、欧洲和世界各地接受不同 EGFR 抑制剂治疗的 NSCLC 和 EGFR 突变患者的更多信息。此外，还需要明确耐药机制、确定克服 EGFR 抑制剂耐药性的方法以及改进抑制剂。该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 体细胞敏化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。对世界各地接受 EGFR 抑制剂治疗的 NSCLC 患者的 EGFR 突变进行的研究将明确欧洲种族背景受试者和那些接受厄洛替尼和吉非替尼治疗的 NSCLC 受试者的 EGFR 突变、治疗反应、无进展生存期和生存期之间的关系。来自东亚。通过研究从对 EGFR 酪氨酸激酶抑制剂具有临床耐药性的患者中收获或建立的肿瘤和肿瘤细胞系，将进行肺癌细胞系的不同治疗方法和对 EGFR 抑制剂获得性耐药模型的实验。这将促进更有效的 EGFR 抑制剂的开发，无论是单独使用还是与其他酪氨酸激酶抑制剂和其他靶向药物一起使用。