Insights into KRAS biology to identify novel therapeutic strategies for cancer
KRAS is one of the most commonly mutated oncogenes in human cancer. Described for the first time more than 40 years ago, KRAS mutations have been considered “undruggable” for decades, till the discovery of inhibitors that selectively target KRAS proteins harboring a glycine-to-cysteine mutation at position 12 (G12C). These drugs were granted accelerated FDA approval in May 2021, nevertheless an urgent need remains for innovative and effective therapeutic strategies to improve outcomes for KRAS cancer patients harboring non-G12C mutations.
A comprehensive understanding of the biological properties of oncogenic KRAS is still incomplete. New approaches and paradigm-shift concepts are urged to find unpredicted vulnerabilities for oncogenic KRAS and eventually pave the way to new therapeutic strategies for KRAS-mutant cancer.