Synthetic Lethal Vulnerabilities in KRAS-Mutant Cancers.

ABSTRACT: KRAS is the most commonly mutated oncogene in human cancer. Most KRAS-mutant cancers depend on sustained expression and signaling of KRAS, thus making it a high-priority therapeutic target. Unfortunately, development of direct small molecule inhibitors of KRAS function has been challenging. An alternative therapeutic strategy for KRAS-mutant malignancies involves targeting codependent vulnerabilities or synthetic lethal partners that are preferentially essential in the setting of oncogenic KRAS. KRAS activates numerous effector pathways that mediate proliferation and survival signals. Moreover, cancer cells must cope with substantial oncogenic stress conferred by mutant KRAS. These oncogenic signaling pathways and compensatory coping mechanisms of KRAS-mutant cancer cells form the basis fo

SUBMITTER: Aguirre AJ 

PROVIDER: S-EPMC5990478 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature