聚焦非小细胞肺癌个体化治疗的新时代.pdfVIP

PROGRESS IN PHARMACEUTICAL SCIENCES 2014,38 3 :231-240 ( ) 231 聚焦非小细胞肺癌：个体化治疗的新时代 汤森路透 [ 摘要 ] 在过去 10 年中，大量靶向药物被研究用于非小细胞肺癌的治疗，目前应用于临床的主要有三类。调节血管内皮生长因子的药物如 安维汀结合细胞毒药物治疗对于提高患者的生存率具有里程碑式的意义，而调节表皮生长因子受体的药物如特罗凯和易瑞沙亦有显著疗效， 并提供了有价值的与疾病相关的生物学信息。ALK 抑制剂在有相关基因易位的患者中展现出良好前景。关键信号通路如 RAS/RAF/MEK、 PI3K/AKT/mTOR 和 MET 激酶的异常也已被确定为重要靶标，尤其对于耐药性患者。针对这些突变者的新型药物目前已应用于临床。靶向 药物和辅助常规肿瘤分析的发展，是通过整合分子水平的研究结果划定患者人群，进而实现非小细胞肺癌真正个体化治疗的实质性的一步。 伴随诊断是个体化给药的关键，自 2009 年起涌现了大量制药公司和诊断试剂公司之间的授权交易，使公司在此领域获得正确的、实用性的 技术。 [ 关键词 ] 非小细胞肺癌；个体化治疗；特罗凯；安维汀；易瑞沙；力比泰 [ 中图分类号 ] R979.1 [ 文献标志码 ] D [ 文章编号 ] 1001-5094(2014)03-0231-09 Spotlight on Non-small-cell Lung Cancer: a New Era in Personalized Care Thomson Reuters [Abstract] Over the past decade, a multitude of targeted agents have been explored in the treatment of non-small-cell lung cancer (NSCLC) and there are now three classes of agents which have been implemented in clinical practice. The VEGF-directed therapy Avastin has shown landmark improvements in survival when added to cytotoxic therapy, while the EGFR-directed therapies Tarceva and Iressa have shown significant benefit and uncovered valuable information about the biology of the disease. Latterly, inhibitors of ALK have also shown great promise in patients with the relevant gene translocation. Aberrations in other key signaling pathways such as RAS/RAF/MEK, PI3K/AKT/mTOR and MET kinase have also been identified as crucial targets, particularly in resistant patients, and novel drugs aimed at these abnormalities are already in the clinic. The development of these targeted agents, alongside routine tumor profiling, is a substantial step toward realizing tru