HRS-4642: The next piece of the puzzle to keep KRAS in check

KRASG12D is the most frequent KRAS mutation in human cancer. In this issue, Zhou et al. describe a novel KRASG12D inhibitor, HRS-4642, that shows potent and selective anti-tumor activity across various models and synergizes with proteasome inhibitors. Responses have also been observed in patients during an ongoing phase 1 trial. KRASG12D is the most frequent KRAS mutation in human cancer. In this issue, Zhou et al. describe a novel KRASG12D inhibitor, HRS-4642, that shows potent and selective anti-tumor activity across various models and synergizes with proteasome inhibitors. Responses have also been observed in patients during an ongoing phase 1 trial. Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancerZhou et al.Cancer CellJune 27, 2024In BriefZhou et al. report the potent preclinical and clinical anti-tumor efficacy of a KRAS G12D-specific inhibitor, HRS-4642, and its sensitizing combinational strategy with carfilzomib. This work provides novel therapeutics for solid tumor patients harboring KRAS G12D mutation, for whom effective targeted therapies are lacking. Full-Text PDF