AXL and c-Met Dual-Targeting in Non-Small Cell Lung Cancer: A Review of Small-Molecule Inhibitors and Their Structure-Activity Relationships.

AXL and c-Met have been identified as pivotal oncogenic factors in non-small cell lung cancer (NSCLC), their downstream signaling pathways exhibit substantial cross-talk, and the simultaneous inhibition of both factors has demonstrated substantial anti-tumor efficacy. Molecular targeted therapy is characterized by its high precision and low toxicity, which confers a significant advantage in the management of NSCLC. Extensive research has explored the co-targeting of AXL and c-Met in both preclinical and clinical contexts, primarily emphasizing small-molecule inhibitors. This review systematically examines the structure, function, regulatory mechanisms, and signaling pathways of AXL and c-Met. It then highlights recent advancements in small molecule co-targeted inhibitors of AXL and c-Met, detailing their mechanisms of action in NSCLC treatment, and summarizes the results of relevant clinical trials. AXL and c-Met significantly influence NSCLC cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), and drug resistance, all of which adversely affect patient prognosis. Co-targeting of AXL and c-Met is considered a promising therapeutic strategy for NSCLC.