Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer.

ABSTRACT: CRISPR-based cancer dependency maps are accelerating advances in cancer precision medicine, but adequate functional maps are limited to the most common oncogenes. To identify opportunities for therapeutic intervention in other rarer subsets of cancer, we investigate the oncogene-specific dependencies conferred by the lung cancer oncogene, RIT1. Here, genome-wide CRISPR screening in KRAS, EGFR, and RIT1-mutant isogenic lung cancer cells identifies shared and unique vulnerabilities of each oncogene. Combining this genetic data with small-molecule sensitivity profiling, we identify a unique vulnerability of RIT1-mutant cells to loss of spindle assembly checkpoint regulators. Oncogenic RIT1^M90I weakens the spindle assembly checkpoint and perturbs mitotic timing, resulting in sensiti

SUBMITTER: Vichas A 

PROVIDER: S-EPMC8352964 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature