作用机制篇安维汀精准靶向VEGF，抑制肿瘤血管生成，持续控制肿瘤安维汀是目前国内唯一拥有二线生存获益的靶向药物安维汀耐受性良好，相关不良反应明确，可预期并可管理主要内容安维汀精准靶向VEGF，抑制肿瘤血管生成，持续控制肿瘤安维汀是目前国内唯一拥有二线生存获益的靶向药物安维汀耐受性良好，相关不良反应明确，可预期并可管理主要内容血管生成是肿瘤生长的关键驱动因素VEGFVEGFbFGFTGF-1VEGFbFGFTGF-1PLGFVEGFbFGFTGF-1PLGFPD-ECGFVEGFbFGFTGF-1PLGFPD-ECGFPleiotrophin1. Bergers G, Benjamin LE. Nat Rev Cancer 2003; 3:401-410.2. Kim KJ, et al. Nature 1993; 362(6423):841-844.3. Folkman. In: DeVita, Hellman, Rosenberg, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.4. Ferrara N, et al. Nat Med 2003; 9(6):669-676.5. Inoue M, et al. Cancer Cell 2002; 1:193-202.6. Mesiano S, et al. Am J Pathol 1998; 153(4):1249-1256.7. Melnyk O, et al. J Urol 1999; 161:960-963.VEGF通过与其受体相互作用而调节肿瘤血管生成VEGFVEGF受体促进现有内皮细胞的存活1,3,4,8,9有助于血管异常化1,3,4,8,10刺激新血管生长1,2,3,4,8,9增加血管通透性11,121. Bergers G, Benjamin LE. Nat Rev Cancer 2003; 3:401-410. 2. Inoue M, et al. Cancer Cell 2002; 1:193-202.3. Ferrara N. Endocr Rev 2004; 25(4):581-611. 9. Hicklin DJ, Ellis LM. J Clin Oncol 2005; 23:1011-1027.10. Baka S, et al. Expert Opin Ther Targets 2006; 10(6):867-876. 11. Morabito A, et al. The Oncologist 2006; 11:753-764. 12. de Vries C, et al. Science 1992; 255:5047-5049. 13. Jain RK. Science 2005; 58:307-312.14. Gerber HP, Ferrara N. Cancer Res 2005; 65:671-680. 15. Jain RK. Nat Med 2001; 7(9):987-990.16. Margolin K. Curr Oncol Rep 2002; 4:20-28. 17. Hu L, et al. Am J Pathol 2002; 161(5):1917-1924.高VEGF水平与不佳的临床预后相关114降低总生存6,12增加疾病进展1,4,9增加复发风险6,8增加血管通透性4预后不良58,14VEGF高水平1. Hicklin DJ, Ellis LM. J Clin Oncol 2005; 23:1011-1027.2. Ferrara N. Endocr Rev 2004; 25(4):581-611.3. Ferrara N, et al. Nat Rev Drug Discov 2004; 3:391-400.4. Margolin K. Curr Oncol Rep 2002; 4:20-28.5. Kaya A, et al. Respir Med 2004; 98:632-636.6. Des Guetz G, et al. Br J Cancer 2006; 94:1823-1832.7. OByrne KJ, et al. Br J Cancer 2000; 82(8):1427-1432.8. Yuan A, et al. Int J Cancer (Pred Oncol) 2000; 89:475-483.9. Imoto H, et al. J Thorac Cardiovasc Surg 1998; 115:1007-1011.10. Galizia G, et al. Clin Cancer Res 2004; 10:3490-3499.11. Ishigami SI, et al. Br J Cancer 1998; 78(10):1379-1384.12. Escudier B, et al. Lancet 2007; 370:2103-2111.13. Hu L, et al. Am J Pathol 2002; 161(5):1917-1924.14. Ferrara N, Davis-Smyth T. Endocr Rev 1997; 18(1):4-25.安维汀精准地靶向于VEGF，抑制血管生成，持续控制肿瘤安维汀VEGF1. Baluk P, et al. Curr Opin Genet Dev 2005; 15:102-111.2. Willett CG, et al. Nat Med 2004; 10(2):145-147.3. OConnor JPB, et al. Clin Cancer Res 2009; 15:6674-6682.4. Mabuchi S, et al. Clin Cancer Res 2008; 14:7781-7789.5. Prager GW, et al. Mol Oncol 2010; 4:150-160.6. Yanagisawa M, et al. Anti-Cancer Drugs 2010; 21:687-694.7. Dickson PV, et al. Clin Cancer Res 2007; 13:3942-3950.安维汀在单纯化疗的基础上提高疗效现有肿瘤血管的退化1-3新血管生长抑制1-4降低存活肿瘤血管的通透性5-7一致提高缓解率7-11持续控制肿瘤生长4,12,13减少腹水和积液2, 3, 5, 14-201. Baluk P, et al. Curr Opin Genet Dev 2005; 15:102-111.2. Willett CG, et al. Nat Med 2004; 10(2):145-147.3. OConnor JPB, et al. Clin Cancer Res 2009; 15:6674-6682.4. Mabuchi S, et al. Clin Cancer Res 2008; 14:7781-7789.5. Prager GW, et al. Mol Oncol 2010; 4:150-160.6. Yanagisawa M, et al. Anti-Cancer Drugs 2010; 21:687-694.7. Dickson PV, et al. Clin Cancer Res 2007; 13:3942-3950.8. Hurwitz H, et al. N Engl J Med 2004; 350:2335-2342. 9. Sandler A, et al. N Engl J Med 2006; 355:2542-2550. 10. Escudier B, et al. Lancet 2007; 370:2103-2111. 11. Miller K, et al. N Engl J Med 2007; 357:2666-2676. 12. Wild R, et al. Int J Cancer 2004; 110:343-351. 13. Gerber HP, Ferrara N. Cancer Res 2005; 65:671-680. 14. Mesiano S, et al. Am J Pathol 1998; 153(4):1249-1256. 15. Hu L, et al. Am J Pathol 2002; 161(5):1917-1924.16. Ribeiro SCC, et al. Respirology 2009; 14:1188-1193.17. Watanabe M, et al. Hum Gene Ther 2009; 20:598-610.18. Bellati F, et al. Invest New Drugs 2010; 28:887-894.19. Huynh H, et al. J?Hepatol 2008; 49:52-60.20. Ninomiya S, et al. J Surg Res 2009; 154:196-202.早期并持续抑制VEGF是mCRC患者重要的治疗策略安维汀一线治疗早期肿瘤控制安维汀持续应用维持肿瘤控制1. Ferrara N, et al. Nat Med 2003; 9(6):669-676. 2. Klement G, et al. J Clin Invest 2000; 105(8):R15-24.3. Klement G, et al. Clin Cancer Res 2002; 8(1):221-232.4. Bennouna J, et al. Lancet Oncol 2012; doi:10.1016/S1470-2045(12)70516-8.5. Massi G, et al. 2012 ESMO Abstract LBA17.6. Grothey A, et al. J Clin Oncol 2008; 26:5326-5334.7. Cohn, et al. WCGC 2010谢谢