肺癌耐药分子标志与个体性化疗课件.pptVIP

靶细胞的选择: 血管内皮细胞 VS 肿瘤细胞 血管内皮细胞基因组较为稳定,不易产生耐药性; 正常成熟组织毛细血管内皮细胞处于静止状态,而肿瘤血管内皮细胞增殖活跃,出现许多相对特异的标记分子,表达较正常静止内皮细胞可高达50倍以上,是潜在的抗肿瘤血管靶向分子; 一个内皮细胞可支持50～100肿瘤细胞的生长。因此针对血管内皮细胞比直接针对肿瘤细胞更为有效; 针对肿瘤血管治疗策略具有抗瘤的广谱性。 重组内皮抑素具有抑制肿瘤组织新生血管生成和直接抑制肿瘤细胞生长及迁移的双重抗肿瘤活性。 抗血管生成化疗药物筛选标准 ①差异的细胞毒性：抑制内皮细胞剂量应低于对肿瘤细胞 ②干扰内皮细胞功能：紫杉醇 ③明确的作用机制：抑制血管生成具体环节 ④体内抑制血管生成：如紫杉醇 抗血管生成化疗显示较强的临床应用价值: ①为常规化疗不敏感或(和) 复发患者的治疗开辟新领域,由于无明显骨髓毒性,也为因体力不支、状态不佳等因素不宜接受常规化疗的患者提供新的治疗方法; ②不存在耐药,可用于常规化疗后耐药患者; ③与传统抗血管生成抑制剂联合疗效更佳; ④与常规化疗、放疗联合可能会使疗效进一步提高。 四. 典型病例 张X，男，57岁,右上肺低分化腺癌并多发性骨转移T3N2M1，Ⅳ 期， MRP(+),p-gp (+), ERCC1(-), RRM1 (+). 治疗前 治疗后 小结与展望 MDR分子机制深入研究将实现对肺癌的发生机制、诊断及化学治疗的突破性。 肺癌患者化疗耐药分子标志基因与化疗疗效之间关系能够尽早得到建立。 根据肺癌患者化疗耐药分子标志，精确选择并制定特异化疗方案，科学调整个体化剂量，实现肺癌个体化性化疗方案疗效的新飞跃。 * * Current first-line chemotherapy options include the combination of a platinum-based agent with paclitaxel, gemcitabine, vinorelbine or docetaxel. Non-platinum-containing regimens are not widely used. Single-agent cisplatin is not generally recommended for use. Docetaxel monotherapy is currently the only approved agent for previously treated NSCLC. Results from studies using these agents (the majority of which contain fewer than 30 patients) range enormously, with objective response rates of 0-38%. Recent studies have investigated the value of newer agents in combination with platinum agents (eg the Eastern Cooperative Oncology Group [ECOG] trial comparing paclitaxel/cisplatin, paclitaxel/carboplatin, docetaxel/cisplatin and gemcitabine/cisplatin).1 Current regimens have limited efficacy and significant toxicity, which results in many patients being either unable or unwilling to undertake chemotherapy, leaving them with no other choice apart from best supportive care. Even docetaxel monotherapy causes ‘substantial toxicity’ (hair loss, low white blood cell count, fatigue) in the majority of patients.2 Median survival in NSCLC patients has improved by only ~2 months over the past 3 decades.3 References Schiller JH, et al. N Engl J Med 2002;