A systems mechanism for KRAS mutant allele-specific responses to targeted therapy.

ABSTRACT: Cancer treatment decisions are increasingly guided by which specific genes are mutated within each patient's tumor. For example, agents inhibiting the epidermal growth factor receptor (EGFR) benefit many colorectal cancer (CRC) patients, with the general exception of those whose tumor includes a KRAS mutation. However, among the various KRAS mutations, that which encodes the G13D mutant protein (KRAS^G13D) behaves differently; for unknown reasons, KRAS^G13D CRC patients benefit from the EGFR-blocking antibody cetuximab. Controversy surrounds this observation, because it contradicts the well-established mechanisms of EGFR signaling with regard to RAS mutations. Here, we identified a systems-level, mechanistic explanation for why KRAS^G13D cancers

SUBMITTER: McFall T 

PROVIDER: S-EPMC6864030 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature