乳腺癌生物靶向治疗进展.pptVIP

Royce slides Japan Oct 2002 Royce slides Japan Oct 2002 乳腺癌生物靶向治疗进展复旦大学肿瘤医院胡夕春 靶向治疗的长处 毒性低、疗效好的治疗手段 个体化 部分病例治愈、部分病例变为慢性病。 靶向的不同层次 器官靶向 直接注入 介入治疗 细胞靶向 细胞摄取, 主动吞噬, 定向 抗原, 单抗导向 双功能抗体 活化T细胞＋瘤抗原 分子靶向 分子生物学差异, 基因, 酶, 信号转导, 细胞分裂, 周期运行 血管生成, 代谢不同等 抗癌药定位到靶细胞的生物大分子或小分子上 可能的靶目标 EGFR 和酪氨酸激酶 可逆抑制剂：ZD 1839 (Gefitinib, Iressa)、OSI 358,774 (Erlotinib, Tarceva) 不可逆抑制剂：CI-1033 (pan-erbB)、EKB 569 (erbB 1 and 2) Her2: herceptin, lapatinib VEGF：Avastin (bevacizumab) Farnesyl Transferase Inhibitors (FTI’s) 法呢基 R115,777 (Tipifarnib, Zarnestra，口服 ) SCH 66336 口服 BMS 214662 口服和静脉 反义核苷酸：G3139 (Genasense, 下调 Bcl-2，促进凋亡) New drugs Lapatinib oral tyrosine kinase inhibitor of ErbB1 and ErbB2 Blocks signaling through EGFR and HER2 homodimers and heterodimers May also prevent signaling between ErbB1/ErbB2 and other ErbB family members 乳腺癌靶向治疗现状 靶向治疗的原则 正常细胞 肿瘤细胞 靶向治疗的原则 正常细胞 肿瘤细胞 Herceptin 成功经验 预后因子 预测因子 Her2 阳性的定义 免疫组化（IHC）和荧光原位杂交（FISH） 定义? IHC 3+ membranous staining = positive IHC 2+/1+ ? FISH (10-25% may be amplified) IHC negative, 5% probability of amplification 靶向治疗失败教训1. Avastin和化疗组合不当 VEGF 促进血管形成 Bevacizumab 理论基础 Tumor growth is dependent on angiogenesis VEGF is a potent stimulator of angiogenesis Bevacizumab is a humanized monoclonal antibody directed against VEGF Recognizes all VEGF-A isoforms Activity as monotherapy in patients with colon cancer or breast cancer Capecitabine plus Bevacizumab: Patient characteristics Capecitabine plus Bevacizumab: Toxicity profile Capecitabine plus Bevacizumab: Response and duration Capecitabine plus Bevacizumab: Progression free survival Bevacizumab ± Paclitaxel for Locally Recurrent or Metastatic Disease PFS significantly longer with combination therapy 10.97 months vs 6.11 months HR = 0.498 (95% CI, 0.401-0.618), P .001 Overall survival significantly higher for patients receiving bevacizumab + paclitaxel vs paclitaxel alone HR = 0.674 (95% CI, 0.495-0.917), P = .01 Overall response significantly better for patients treated