KRAS oncogene in lung cancer: focus on molecularly driven clinical trials

摘要: KRAS mutations are the most frequent molecular abnormalities found in one out of four nonsmall cell lung cancers (NSCLC). Their incidence increases cases adenocarcinoma, smokers and Caucasian patients. negative value terms prognosis responsiveness to both standard chemotherapy targeted therapies remains under debate. Many drugs have been developed specifically for KRAS-mutated NSCLC Direct inhibition RAS activation failed show any clinical efficacy. Inhibition downstream targets mitogen-activated protein kinase (MEK) pathway is a promising strategy: phase II combinations MEK 1/2 inhibitors with doubled patients' outcomes. One III trial such setting ongoing. Double epidermal growth factor receptor proteins currently being assessed early-phase trials. The association mammalian target rapamycin leads non-manageable toxicity. Other strategies, as heat-shock 90 or focal adhesion assessed. Abemaciclib, cyclin-dependent 4/6 inhibitor, showed results I trial, 54% disease control rate. Results an ongoing warranted. Immunotherapy might be next relevant step management due high burden associated neo-antigens.