A novel inhibitor for KRASG12C mutant lung carcinoma

Abstract

Mutations in KRAS are among the most common aberrations in cancer. However, despite considerable research efforts, KRAS remains a challenging therapeutic target. In recent years, there has been a drive to develop KRAS mutant specific drugs. Among the different known mutations, the KRASG12C (glycine 12 to cysteine) has been considered druggable. Studies have shown that due in part to the close proximity of Cysteine 12 to both the nucleotide pocket and the switch regions, thiol-reactive compounds can bind to the active site covalently and inhibit KRASG12C mutation-driven signaling. The absence of this particular cysteine residue in wild-type KRAS makes such an approach very selective towards cancer cells.