课件：爱必妥作用机制及不良反应处理.ppt

* EGFR大体由三部分组成：细胞表面受体，跨膜蛋白，细胞内的酪氨酸激酶。配体与细胞表面的受体结合后，将信号传导至细胞核内，影响基因转录/细胞周期进程，从而影响肿瘤细胞的生存、增殖、血管生成、转移等。 Her 受体通过酪氨酸激酶活化后引起胞内信号的传导,并最终导致基因的激活和细胞的分裂。 * - 已经发现人类的多种肿瘤细胞都表达EGFR。.[1-15] The increased level of expression found in many tumor types and its consequences on tumor growth provide the rationale for targeting the EGFR in cancer therapy. - EGFR在各肿瘤中表达水平高低不同，有很大的差异. 在某些肿瘤类型中，EGFR的表达是很普遍的。比如头颈部鳞癌。. - Variation in EGFR expression observed within studies of a given tumor type could be due in part to a lack of consistency in detection methods, inherent biological differences between tumors, and/or stage of disease. - 高表达的受体也会导致配体的高表达。 (EGF, TGF-alpha). - EGFR expression has been correlated with increased resistance to certain chemotherapeutic agents and radiotherapy. - Substantial evidence exists for increased EGFR expression in multiple tumor types. 1. Salomon DS, Brandt R, Ciardiello F, Normanno N. Crit Rev Oncol Hematol 1995;19:183-232. 2. Messa C, Russo F, Caruso MG, Di Leo A. Acta Oncol 1988;37:285-289. 3. Grandis JR, Melhem MF, Barnes EL, Tweardy DJ. Cancer 1996;78:1284-1292. 4. Uegaki K, Nio Y, Inoue Y, et al. Anticancer Res 1997;17:3841-3847. 5. Fujino S, Enokibori T, Tezuka N, et al. Eur J Cancer 1996;32A:2070-2074. 6. Fontanini G, DeLaurentiis M, Vignati S, et al. Clin Cancer Res 1998;4:241-249. 7. Yoshida K, Hosoya Y, Sumi S, et al. Oncology 1997;54:220-225. 8. Klijn JG, Berns PM, Schmitz PI, Foekens JA. Endocr Rev 1992;13:3-17. 9. Bucci B, DAgnano I, Botti C, et al. Anticancer Res 1997;17:769-774. 10. Walker RA, Dearing SJ. Breast Cancer Res Treat 1999;53:167-176. 11. Bartlett JM, Langdon SP, Simpson BJ, et al. Br J Cancer 1996;73:301-306. 12. Fischer-Colbrie J, Witt A, Heinzl H, et al. Anticancer Res 1997;17:613-619. 13. Watanabe K, Tachibana O, Sata K, et al. Brain Pathol 1996;6:217-223. 14. Rieske P, Kordek R, Bartkowiak J, et al. Pol J Pathol 1998;49:145-149. 15. Chow NH, Liu HS, Lee EI, et al. Anticancer Res 1997;17:1293-1296. * - 实验证明，肿瘤细胞对放化疗产生耐受与EGF