贝伐珠单抗抗血管机制[宣讲].pptVIP

* 获得性耐药，很大程度上由于基因不稳定（基因突变、扩增、缺失等），而作用于微环境的抗血管药物很少出现有获得性耐药3 * 人结肠癌(SW620，使用抗VEGF抗体B20-4.1和B20-4.1.1作为贝伐珠单抗的替代品 * * * * Avastin has demonstrated to increase survival (either PFS or OS) in 6 different tumor types including Ovarian cancer, where we reported two positive phase III studies in 2010 (GOG 218 and ICON-7). Ovarian cancer has been filed in the EU and the US filing is planned for Q4’2011. Last year we also reported that trials in Prostate, Gastric and adjuvant Colon Cancer missed their primary endpoints. * 抗血管生成药物在控制肿瘤中的价值 内容 抗血管生成是治疗肿瘤的关键因素 贝伐珠单抗精准地靶向于VEGF，通过多种作用控制肿瘤 贝伐珠单抗持续应用，持续抑制血管生成，维持肿瘤控制 * 抗血管生成是治疗肿瘤的关键因素 在多个肿瘤类型中，血管生成是肿瘤发生发展的关键驱动因素1 肿瘤直径2mm时，其存活与生长需要独立的血液供应 1–4 肿瘤血管生成，为肿瘤细胞提供血氧，使肿瘤不断发展、转移 1. Folkman. In: Kufe, Pollock, Weichselbaum, eds. Cancer Medicine(Holland). 6th ed. Hamilton, Ontario: BC Decker; 2000; 2. Bergers, Benjamin. Nat Rev Cancer 2003; 3.?Folkman. NEJM 1971; 4. Folkman. J Natl Cancer Inst 1990 肿瘤 血管 * 影响临床疗效的重要原因之一是肿瘤组织血管异常 肿瘤内血管系统结构异常 1. Jain, et al. Nat Med 2001; 2. Carmeliet, et al. Nat Rev Drug Discov 2011 肿瘤内血管壁的细胞功能异常1,2 有效药物无法到达肿瘤组织 Week 11 Week 13 Week 16 A 正常血管 B 异常血管 * 血管生成的关键调节因素是VEGF和其受体的相互作用1–5，高VEGF水平与不佳的临床预后相关6–19 1. Ferrara. Endocr Rev 2004; 2. Hicklin, Ellis. JCO 2005; 3. Baka, et al. Expert Opin Ther Targets 2006; 4. Morabito, et al. Oncologist 2006; 5. de Vries, et al. Science 1992; 6.?Bergers, Benjamin. Nat Rev Cancer 2003; 7. Jain. Science 2005; 8. Gerber, Ferrara. Cancer Res 2005; 9. Jain. Nat Med 2001; 10. Inoue, et al. Cancer Cell 2002; 11. Margolin. Curr Oncol Rep 2002; 12. Hu, et al. Am J Pathol 2002，1.Hicklin, Ellis. JCO 2005; 2. Ferrara. Endocr Rev 2004; 3. Ferrara, et al. Nat Rev Drug Discov 2004; 4. Margolin. Curr Oncol Rep 2002; 5. Kaya, et al. Respir Med 2004; 6. Des Guetz, et al. Br J Cancer 2006; 7. O’Byrne, et al. Br J Cancer 2000; 8. Yuan, et al. Int J Cancer(Pred Oncol) 2000; 9. Imoto, et al. J Thorac Cardiovasc Surg 1998; 10. Galizia, et al. Clin Cancer Res 2004; 11. Ishigami, et al. Br J Cancer