Clinical significance of MET alterations in non-small cell lung cancer and currently available therapies

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality both in Russia and worldwide. At diagnosis, most patients have advanced disease when the use of local treatment modalities is limited and systemic chemotherapy fails to provide a pronounced and sustained benefit. The advent of targeted therapies has significantly changed the treatment paradigm of NSCLC. Genetic alterations representing potential molecular targets have been identified in up to 60 % of non-squamous NSCLC cases, and agents directed against 50 % oncogenic targets have been approved. Various activat ing mutations of the MET signaling pathway (gene amplifications and alterations) associated with unfavorable disease outcomes occur in 2-4 % of NSCLC patients. Recently, significant advances in the development of therapies targeting this signaling pathway have been made. The article provides an overview of the key studies evaluating novel therapeutic options for NSCLC with MET alterations.