Evolving MET-Directed Therapies in NSCLC: From Present Treatment to Innovative Future Approaches

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide.Despite significant advances in chemotherapy, targeted therapy, and immunotherapy, patient outcomes often remain poor.Among emerging molecular targets, the mesenchymal-epithelial transition (MET) factor has garnered increasing attention for its role in tumorigenesis, driven by exon 14 skipping mutations, gene amplification, and point mutations that dysregulate key signaling pathways such as PI3K-AKT and RAS-MAPK.In this review, we provide a comprehensive overview of MET alterations in NSCLC, detailing the molecular mechanisms underlying these events and tracing the evolution of MET-targeted therapeutics-from early multi-kinase inhibitors to second-generation agents with enhanced specificity.We also examine innovative modalities such as antibody-drug conjugates, bispecific antibodies, and proteolysis-targeting chimeras (PROTACs), highlighting their capacity to improve response rates and mitigate resistance.By summarizing these major therapeutic categories, our review offers an accessible perspective on current trends and future directions in MET-driven NSCLC, emphasizing the critical need for continued research into personalized treatment strategies.