课件：肺癌的生物靶向治疗进展.pptVIP

* * * * * * A tumour needs to establish new vasculature to obtain the nutrients necessary to sustain growth beyond 1-2 mm3. Angiogenesis is defined as the development of new capillaries from existing vessels. Tumours induce angiogenesis by increasing production and secretion of angiogenic factors and proteases that act in concert to promote angiogenesis. Secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF) increase endothelial-cell-associated protease activity and stimulate endothelial cell migration and proliferation. Proteases secreted by tumour cells and endothelial cells degrade the extracellular matrix, allowing endothelial cell migration. Together these processes promote angiogenic sprouting and the formation of new tumour vasculature. New vessels formed during pathological angiogenesis, compared with those produced normally, are not well formed and are described as tortuous and leaky. Therapeutic inhibition of tumour angiogenesis should be effective in all solid malignancies and the biological effect should be tumour specific, as, apart from the female reproductive system, angiogenesis is quiescent in healthy tissues. Furthermore, genetically stable endothelial cells may be less prone to developing drug resistance than tumour cells. Drug delivery is facilitated because target tissue is in direct contact with blood. Tumour vasculature may be targeted by: preventing new blood vessel growth (angiogenesis inhibition) destroying existing tumour blood vessels (vascular targeting). Angiogenesis inhibition is potentially complementary to other antitumour strategies. * TRIBUTE 的疗效与毒副反应 Tarceva Placebo HR P-值 MST 10.8m 10.6m 0.99 0.95 OR% 21.5 19.3 -- 0.36 OR 时间 5.5m 5.0m 0.85 .032 TTP 5.1m 4.9m 0.94 0.36 总体副反应 99.5% 99.5% G3/4腹泻与皮疹 47.7% 43.2% SAE死亡 53 27 THANK YOU SUCCESS * * 可编辑 TRIBUTE的亚组分析 单因素分析: 分期,体重下降, 年龄, 性别,种族,PS, EGFR状态,组织学类型不能预测病人对Tarceva的反应 不吸烟者A组 MST(44例)为23月,相同对照组为10月,HR 0.49, 95%CI 0.28-0.85 Miller, et al.