KRAS-G12C covalent inhibitors: A game changer in the scene of cancer therapies.

RAS is the most frequently mutated oncogene in human cancer. Scientists attempted for decades to target this protein or its pathways, however, all the attempts failed and RAS was labeled as "undruggable". With KRAS-G12C covalent inhibitors entering clinical trials, the myth of this "undruggable" RAS is fading away. In 2021, the Food and Drug Administration (FDA) approved the use of Sotorasib (Lumakras) for the treatment of adult patients with KRAS-G12C mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy. However, and as every other drug, KRAS-G12C inhibitors are facing intrinsic and acquired resistances. In order to overcome these resistances, researchers are now working on combination strategies. Furthermore, studies are currently ongoing to better elucidate the status of KRAS-G12C as a predictive and prognostic tool and to strengthen its role in the field of personalized medicine.