谢
谢
安维汀精准地靶向于VEGF，抑制血管生成，持续控制肿瘤
VEGF
安维汀
1. 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. O’Connor 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-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, 14-20
1. 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. O’Connor 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.
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.
VEGF通过与其受体相互作用而调节肿瘤血管生成
VEGF
VEGF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11,12
1. 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.
作用机制篇
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
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
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.
血管生成是肿瘤生长的关键驱动因素
VEGF
VEGF
bFGF TGFβ-1
VEGF
bFGF TGFβ-1 PLGF
VEGF
bFGF TGFβ-1 PLGF PD-ECGF
VEGF
bFGF TGFβ-1 PLGF PD-ECGF Pleiotrophin
1. 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.
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
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.
高VEGF水平与不佳的临床预后相关1–14
降低总生存6,12 预后不良5–8,14
增加疾病进展1,4,9
VEGF高水平
增加复发风险6,8
增加血管通透性4
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. O'Byrne KJ, et al. Br J Cancer 2000; 82(8):1427-1432.