Targeting KRAS-Mutant Non–Small-Cell Lung Cancer: One Mutation at a Time, With a Focus on KRAS G12C Mutations
Cet article passe en revue les données épidémiologiques concernant le cancer du poumon avec mutation du gène KRAS, analyse l'association entre des mutations du gène KRAS (dont la mutation G12C) et la survie globale puis présente les approches thérapeutiques actuelles
Key Objective : To provide an overview of the epidemiology and prognostic and predictive value of KRAS mutations in non–small-cell lung cancer (NSCLC), summarizing current treatment approaches and highlighting unmet needs.
Knowledge Generated : Specific RAS mutations can render RAS proteins constitutively active, resulting in uncontrolled cell proliferation. KRAS-mutated NSCLC is heterogeneous. KRAS G12C is the most prevalent of the KRAS mutations. KRAS mutations, particularly KRAS G12C, are indicative of poor overall survival, with comutational status also affecting prognosis. Therapies targeting KRAS are beginning to show clinical potential, most notably with KRASG12C inhibitors. Strategies for KRASG12C inhibition are discussed.
Relevance : In Western populations, KRAS mutations are one of the most common oncogenic drivers in NSCLC, with KRAS G12C mutation representing nearly half of KRAS mutations. KRAS inhibition offers potential for targeted treatment of NSCLC; KRASG12C inhibitors are under clinical development and may represent an effective therapeutic option for patients with NSCLC.
Journal of Clinical Oncology , résumé, 2019