TY - JOUR T1 - <em>KRAS</em> oncogene in lung cancer: focus on molecularly driven clinical trials JF - European Respiratory Review JO - EUROPEAN RESPIRATORY REVIEW SP - 71 LP - 76 DO - 10.1183/16000617.0071-2015 VL - 25 IS - 139 AU - Emmanuelle Kempf AU - Benoît Rousseau AU - Benjamin Besse AU - Luis Paz-Ares Y1 - 2016/03/01 UR - http://err.ersjournals.com/content/25/139/71.abstract N2 - KRAS mutations are the most frequent molecular abnormalities found in one out of four nonsmall cell lung cancers (NSCLC). Their incidence increases in cases of adenocarcinoma, smokers and Caucasian patients. Their negative value in terms of prognosis and responsiveness to both standard chemotherapy and targeted therapies remains under debate. Many drugs have been developed specifically for KRAS-mutated NSCLC patients. Direct inhibition of RAS activation failed to show any clinical efficacy. Inhibition of downstream targets of the mitogen-activated protein kinase (MEK) pathway is a promising strategy: phase II combinations of MEK 1/2 kinase inhibitors with chemotherapy doubled patients’ clinical outcomes. One phase III trial in such a setting is ongoing. Double inhibition of MEK and epidermal growth factor receptor proteins is currently being assessed in early-phase trials. The association with mammalian target of rapamycin pathway inhibition leads to non-manageable toxicity. Other strategies, such as inhibition of molecular heat-shock proteins 90 or focal adhesion kinase are currently assessed. Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, showed promising results in a phase I trial, with a 54% disease control rate. Results of an ongoing phase III trial are warranted. Immunotherapy might be the next relevant step in KRAS-mutated NSCLC management due to the high burden of associated mutations and neo-antigens.MEK inhibition and immunotherapy are very promising therapeutic advances in KRAS-mutated nonsmall cell lung cancer http://ow.ly/U2ohp ER -