Synthetic Vulnerabilities in the KRAS Pathway.

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.