遗传学和生物标志物在个性化肺癌治疗中的作用
Rafael Rosell1, Trever G Bivona, Niki Karachaliou
1Catalan Institute of Oncology Badalona, Spain. rrosell@iconcologia.net
Lancet (London, England)
|August 27, 2013
概括
针对非小细胞肺癌 (NSCLC) 的向疗法有希望,但往往是短暂的. 了解抵抗机制,如EGFR Thr790Met突变和AXL过度表达,是开发有效组合治疗的关键.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 非小细胞肺癌 (NSCLC) 经常出现在转移阶段,平均存活时间仅为一年.
- 皮表皮生长因子受体 (EGFR) 驱动突变是肺腺癌的一个子集中的关键致癌事件,可实现向治疗.
- EGFR氨酸激酶抑制剂 (TKIs) 在大约60%的患者中诱导缓解,但反应通常是暂时的.
研究的目的:
- 研究EGFR突变非小细胞肺癌中对EGFR氨酸激酶抑制剂的耐药性机制.
- 确定新的生物标志物和潜在的组合疗法,以克服治疗耐药性.
主要方法:
- 预先存在的EGFR Thr790Met突变作为暂时反应的潜在驱动因素的分析.
- 调查AXL过度表达和MED12功能作为TKI耐药性的标志.
- 探讨信号通路交叉声作为一种阻力机制.
主要成果:
- EGFR Thr790Met突变可能导致对TKI的短暂反应.
- 过度表达AXL和降低MED12功能与EGFR突变NSCLC中对TKI的耐药性有关.
- 信号通路交叉是另一种重要的阻力机制.
结论:
- 识别参与抗药性途径的分子成分可以指导组合疗法的开发.
- 与EGFR TKI单独治疗相比,对多个分子进行共同向可能会改善治疗结果.
- 序列rebiopsies的深度测序具有识别新生物标志物的潜力.
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