Roman Marta, Hwang Elizabeth, Sweet-Cordero E Alejandro
Department of Pediatrics, University of California San Francisco, San Francisco, CA 94158, USA.
Cancers (Basel). 2022 Jun 8;14(12):2837. doi: 10.3390/cancers14122837.
Mutations in viral oncogene ( are among the most frequent gain-of-function genetic alterations in human cancer. Most -driven cancers depend on its sustained expression and signaling. Despite spectacular recent success in the development of inhibitors targeting specific alleles, the discovery and utilization of effective directed therapies for -mutant cancers remains a major unmet need. One potential approach is the identification of -specific synthetic lethal vulnerabilities. For example, while -driven oncogenesis requires the activation of a number of signaling pathways, it also triggers stress response pathways in cancer cells that could potentially be targeted for therapeutic benefit. This review will discuss how the latest advances in functional genomics and the development of more refined models have demonstrated the existence of molecular pathways that can be exploited to uncover synthetic lethal interactions with a promising future as potential clinical treatments in -mutant cancers.
病毒癌基因中的突变是人类癌症中最常见的功能获得性基因改变之一。大多数由其驱动的癌症依赖于其持续表达和信号传导。尽管最近在开发针对特定等位基因的抑制剂方面取得了显著成功，但针对由其突变驱动的癌症的有效定向疗法的发现和应用仍然是一个重大的未满足需求。一种潜在的方法是识别由其特异性的合成致死弱点。例如，虽然由其驱动的肿瘤发生需要激活许多信号通路，但它也会触发癌细胞中的应激反应通路，这些通路有可能成为治疗靶点从而带来益处。本综述将讨论功能基因组学的最新进展以及更精细模型的开发如何证明了分子通路的存在，这些通路可被利用来揭示合成致死相互作用，作为由其突变驱动的癌症潜在临床治疗方法有着光明的未来。
