安维汀抗血管机制.ppt

* * * * Jain. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7:987–9. Carmeliet, et al. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 2011;10:417–27. * * * * * * * * * * * * * * * * 安维汀抗血管生成控制肿瘤机制 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 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 * VEGF和其受体相互作用调节血管生成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 1998; 12. Escudier, et al. Lancet 2007; 13. Hu, et al. Am J Pathol 2002; 14. Ferrara, Davis-Smyth. Endocr Rev 1997 VEGF VEGF受体 促进现有内皮细胞的存活1,2,6–8 有助于血管异常化1,2,6,7,9 VEGF配体与VEGF受体的相互作用是血管生成的关键调节因素 刺激新血管生长1,2,6–8,10 增加血管通透性11,12 影响临床疗效的重要原因之一是肿瘤组织血管异常 肿瘤内血管系统排列和机构异常 1. Jain, et al. Nat Med 2001; 2. Carmeliet, et al. Nat Rev Drug Discov 2011 a) 异常血管 b) 正常血管 c) 正常化的肿瘤血管 肿瘤内血管壁的细胞功能也是异常的1,2 抑制VEGF可以逆转其中部分异常血管1、2 贝伐珠单抗精准靶向VEGF，抑制血管生成，持续控制肿瘤1,2 * 贝伐珠单抗 VEGF 受体 VEGF 1. Avastin Summary of Product Characte