Targeted Therapies Modulating Mesenchymal–Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib

The mesenchymal-epithelial transition/plasticity (MET/EMP) axis is a key regulator of tumor development, cancer progression, and resistance to therapy, making it an attractive target for intervention. This review highlights strategies to modulate MET/EMP using three representative agents-capmatinib, bemcentinib, and galunisertib-each acting on distinct signaling pathways. Capmatinib is a selective MET tyrosine kinase inhibitor with notable efficacy in non-small cell lung cancer harboring MET exon 14 skipping mutations. Bemcentinib blocks AXL receptor tyrosine kinase, interfering with AXL/GAS6 signaling that promotes tumor survival, metastasis, and therapeutic resistance. Galunisertib inhibits TGF-β signaling, reducing epithelial-mesenchymal transition (EMT), immune evasion, and metastatic potential. We discuss their mechanisms of action, therapeutic applications, and current clinical progress. Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types.