EGFR突变型NSCLC肿瘤内异质性的模式及相关分子机制研究

项目名称： EGFR突变型NSCLC肿瘤内异质性的模式及相关分子机制研究

项目编号： No.81330062

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 王洁

作者单位： 北京大学

项目金额： 290万元

中文摘要： 肺癌以其高发病率和死亡率成为世界上最具挑战性的肿瘤。近年肺癌研究的重要进展之一是发现肿瘤组织内存在各种亚克隆即肿瘤内异质性，其在表型、遗传学或表观遗传学上均存在一定差异，从而导致其功能和生物学行为的不同并在肿瘤复发、转移和耐药中扮演重要的角色。本课题组前期工作发现EGFR突变在化疗后会发生动态改变，而肿瘤内EGFR突变的异质性则可能是此改变的分子基础。基于此，本项目拟以EGFR突变型非小细胞肺癌为研究对象,进一步探寻EGFR突变型肺癌瘤内异质性的模式、动态变化规律及潜在分子机制，通过建立并验证肿瘤内异质性的模式，探讨EGFR敏感与耐药基因的动态、定量检测体系，探寻个体化干预手段、建立异质性基础上的个体化诊疗体系。在此基础上，研究肿瘤异质性及表型转化的相关分子机制，为NSCLC靶向治疗的精确诊断、预测预后和优化治疗策略提供依据。

中文关键词： C05_气管；支气管；肺肿瘤;EGFR突变;肿瘤细胞异质性;分子机制;表皮生长因子受体酪氨酸激酶抑制剂

英文摘要： Treatment of lung cancer is very challenging for its high incidence rate and mortality, one of the most amazing advancement of which recently is tumor heterogeneity in different subclones. The tumor heterogeneity exists in genetics, epigenetic and phenotype et al., leading to difference in biological behavior, function, also playing a key role in tumor recurrence, metastasis and drug resistance. Therefore, tumor heterogeneity becomes more and more decisive in diagnosis and treatment of non-small cell lung cancer (NSCLC). Our previous study found EGFR (epidermal growth factor receptor) mutations status may occur alteration after chemotherapy, which might derive from intratumor heterogeneity. Based on this phenomenon, we propose to further explore the patterns of tumor heterogeneity in EGFR mutant NSCLC and to investigate their dynamic changes in the process of disease treatment and potential molecular mechanism. This project will also establish dynamic and quantitative molecular platforms to detect EGFR-TKIs related sensitive and resistant genes and explore individual interventions; expect to establish individual treatment system based on tumor heterogeneity. Meanwhile, identifying molecular mechanisms related with intratumor heterogeneity and phenotype alteration will provide theoretical basis for accurate molecular diagnosis, outcome predicting and optimized targeted therapeutic strategy.

英文关键词： non-small cell lung cancer;EGFR mutation;tumor heterogeneity;molecular mechanism;EGFR-TKI