Parameswaran Sreejit, Kundapur Deeksha, Vizeacoumar Frederick S, Freywald Andrew, Uppalapati Maruti, Vizeacoumar Franco J
Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, S7N 5E5, Canada; These authors contributed equally.
Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, S7N 5E5, Canada.
Trends Cancer. 2019 Jan;5(1):11-29. doi: 10.1016/j.trecan.2018.11.001. Epub 2018 Dec 7.
Targeted therapies rely on the genetic and epigenetic status of the tumor cells and are seen as the most promising approach to treat cancer today. However, current targeted therapies focus on directly inhibiting those molecules that are altered in tumor cells. Unfortunately, targeting these molecules, even with specific inhibitors, is challenging as tumor cells rewire their genetic circuitry to eliminate genetic dependency on these targets. Here, we describe how synthetic lethality approaches can be used to identify genetic dependencies and develop personalized targeted therapies. We also discuss strategies to specifically target these genetic dependencies, using small molecule and biologic drugs.
靶向治疗依赖于肿瘤细胞的基因和表观遗传状态，被视为当今治疗癌症最有前景的方法。然而，目前的靶向治疗侧重于直接抑制肿瘤细胞中发生改变的那些分子。不幸的是，即使使用特异性抑制剂来靶向这些分子也具有挑战性，因为肿瘤细胞会重新连接其基因回路以消除对这些靶点的基因依赖性。在此，我们描述了如何利用合成致死方法来识别基因依赖性并开发个性化靶向治疗。我们还讨论了使用小分子和生物药物特异性靶向这些基因依赖性的策略。
