肺癌的规范化和个体化治疗.pptVIP

* * Irinotecan used for colorectal cancer * * * * * * * Numerous difficulties to overcome, including: distinguishing between prognostic and predictive value obtaining suitable samples of good quality ensuring standardisation of testing procedures validation through clinical trials required at all stages * RRM1 和ERCC1 是决定早期NSCLC术后生存的决定因子. 预后因子 完全性切除术后的NSCLC患者，如果ERCC1阴性，能从辅助化疗中获益，而ERCC1阳性者则不能获益 预测因子 患者签署基因研究知情同意书 预后好子集 预后差子集 寻找预测因子：学习集 寻找预测因子：证实集 预测因子低表达组 预测因子高表达组 两组分别随机：得到4组 干预组 干预组 对照组 对照组 队列研究：寻找预后因子 未来临床实践中的生物标志物:个体化医学的应用 患者药物反应 ≈ 疾病的基因标志 + 生物标志物 (有效性, 毒性) N1+N2 + 药物标志物 基因 Conc IC95 + 影像标志物 存在疾病? 存在受体亚型? 细胞, 蛋白, 抗体, 小的代谢化学物, 生理指标 同有效性和毒性等终点指标联系起来 2D6 cypP450 genotype [药物]plasma(free) 90%的抑制浓度 如抗病毒的蛋白酶抑制剂 PET, MRI,.. 物理学改变的直接证据 或这是一个管理和治疗的恶梦？ 结论 鉴别和确定生物标志物是需要花费多年时间的复杂过程 NSCLC的生物标志物仍然面临着许多困难 生物标志物指导的靶向个体化治疗将大大改善患者的结果 * * * * * * * * * * ADCC, antibody-dependent cellular cytotoxicity; EGFR, epidermal growth factor receptor * * Within treatment group comparison showed that progression-free survival was significantly longer in mutation positive patients receiving gefitinib (HR 0.19; 95% CI 0.13, 0.26; p0.0001). Within treatment group comparison also showed that progression-free survival was longer in mutation positive patients receiving carboplatin/paclitaxel, but this did not reach significance (HR 0.78; 95% CI 0.57, 1.06, p=0.1103). * * * * In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGF-R) which is expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, non-smokers and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.[22] Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients[89] and has rece