非小细胞肺癌分子靶向治疗.ppt

多西他赛序贯EGFR TKI：有效模式 SATURN研究:特罗凯序贯治疗难以手术的NSCLC患者 [slide 2] BAY 43-9006: A Novel Signal Transduction Inhibitor That Combines Two Anticancer Activities1 BAY 43-9006 is a novel signal transduction inhibitor that in preclinical models prevents tumor growth by combining two anticancer activities: inhibition of tumor cell proliferation and tumor angiogenesis. BAY 43-9006 inhibits tumor cell proliferation by targeting the RAF/MEK/ERK pathway at the level of RAF kinase. BAY 43-9006 also exerts an antiangiogenic effect by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR and their associated signaling cascades. BAY 43-9006 是一种新型的信号转导抑制剂，其联合两种抗癌方式: 在临床前药理模型显示其通过联合抑制肿瘤细胞增殖和抗肿瘤血管生成两种方式来抑制肿瘤生长. BAY 43-9006通过作用于RAF激酶来 2. BAY 43-9006还通过作用于受体酪氨酸激酶血管内皮生长因子受体-2（ VEGFR-2 ）和血小板衍生生长因子受体PDGFR及其所关联的信号瀑布。也在抗血管生成上发挥作用 Reference: 1. Wilhelm S, Carter C, Tang LY, et al. BAY 43-9006 exhibits broad spectrum anti-tumor activity and targets Raf/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Clin Can Res. 2003;9 (suppl). Abstract A78. In preparation for cliical testing, the murine Ab used in the animal studies was humanized to minimize immunogenicity. As you can see from this cartoon, the entire Ab has been humanized with the exception of a small fraction in the variable region. The antibody binds all isoforms of VEGF A with high affinity and has terminal half life of 2-3 wks 2 * EML4-ALK 融合基因--NSCLC 1. Koivunen, et al. Clin Cancer Res 2008 2. Shaw, et al. ASCO 2009 3. Bang, et al. ASCO 2010 3–7% 的NSCLC 患者具有EML4-ALK 融合基因1 目前已有检测的技术 腺癌患者居多(EGFR未有突变者多见)2 Crizotinib的临床 I/II 期研究, 对于选择性的患者: DCR = 70%3 未来对于NSCLC的个体化治疗起到重大的影响 晚期NSCLC 患者 2007年12月－2010年2月 I期研究扩展组中使用克唑替尼，ALK+ （n＝82） I期研究对照组中未使用克唑替尼，ALK+ (n=37) OS评估 (数据截止至 2011年3月15日) 研究设计 某中心筛选的ALK-/EGFR- （n＝253） ALK+ 克唑替尼组（n＝82） ALK+对照组(n=37) ALK- 对照组 (n=37) A. T. Shaw, et,al,2011,ASCO,oral abstract session,7507# 研究结果(OS) ALK＋克唑替尼治疗组(n＝82) ALK＋对照组(n＝37) 1年OS率(%)