mTOR抑制剂治疗非小细胞肺癌疗效预测初步分析  

Effects of mTOR inhibitor on Non-small cell lung carcinoma:a pilot study

作　　者：周海榆[1,2] 陈刚[1,2] 唐继鸣[1,2] 贲晓松[1,2] 谢亮[1,2] 张冬坤[1,2] 叶雄[1,2] 周子浩[1,2] 

机构地区：[1]广东省医学科学院/广东省人民医院 [2]南方医科大学附属华南医院肿瘤中心胸外科,广东广州510080

出　　处：《广州医学院学报》2013年第2期79-83,共5页Academic Journal of Guangzhou Medical College

基　　金：广东省医学科研基金项目(B2010004)

摘　　要：目的:讨RAD001治疗的晚期非小细胞肺癌(NSCLC)患者的疗效及其与nTOR通路相关分子表达水平的关系。方法:收集2009年5月至2009年12月广东省人民医院Ⅰ期临床试验中8例经RAD001治疗NSCLC患者的肿瘤组织和血浆标本,采用免疫组化方法、实时荧光定量方法结合临床资料分析mTOR通路相关分子与疗效之间的可能预测关系。结果:8例NSCLC患者中达到部分缓解(PR)1例、病情稳定(SD)3例、病情进展(PD)3例、不能评价1例(未及评价期死亡患者),中位无进展生存时间(PFS)15周。GOLPH2、mTOR、ALK、KRAS等可考虑为mTOR抑制剂的潜在预测指标;治疗前血浆中部分通路分子mRNA表达水平低的患者对mTOR抑制剂疗效较好。结论:RAD001治疗NSCIC有一定疗效,治疗前血浆部分mTOR通路相关分子mRNA低表达可能提示患者对mTOR抑制剂敏感。Objective： To determine the efficacy of RADO01 and its correlation with mTOR pathway molecular expression in patients with advanced non-small cell lung carcinoma （NSCLC）. Methods： We enrolled 8 patients with NSCLC who underwent a phase 1 RAD001 clinical trial in Guangdong General Hospital between May and December 2009. This entailed determination of the correlation between mTOR pathway-associated molecules and the efficacy via immunohistochemistry and real-time fluorescent quantitative assay on the tumor tissues and plasma specimens. Results ： Of the 8 patients enrolled in the study, 1 had partial remission, 3 stable disease, 3 progression of disease and 1 unavailable assessment （ death tolls excluded）. The mean progression- free survival was 15 weeks. Potential predictive indices of efficacy of mTOR inhibitors included GOLPH2, mTOR, ALK and k-ras expression. Patients with attenuated mRNA expression of mTOR pathway molecules in the plasma showed a preferable response to the treatment. Conclusion： RAD001 is effective in patients with NSCLC. Attenuated plasma mTOR pathway molecule mRNA expression suggests a preferable response to mTOR inhibitors.

关 键 词：非小细胞肺癌 GOLPH3 MTOR RAD001 疗效预测 

分 类 号：R734.1[医药卫生—肿瘤]