Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer.

Breast cancer is the most common malignancy among women, posing a formidable health challenge worldwide. In this complex landscape, the c-MET (cellular-mesenchymal epithelial transition factor) receptor tyrosine kinase (RTK), also recognized as the hepatocyte growth factor (HGF) receptor (HGFR), emerges as a prominent protagonist, displaying overexpression in nearly 50% of breast cancer cases. Activation of c-MET by its ligand, HGF, secreted by neighboring mesenchymal cells, contributes to a cascade of tumorigenic processes, including cell proliferation, metastasis, angiogenesis, and immunosuppression. While c-MET inhibitors such as crizotinib, capmatinib, tepotinib and cabozantinib have garnered FDA approval for non-small cell lung cancer (NSCLC), their potential within breast cancer therapy is still undetermined. This comprehensive review embarks on a journey through structural biology, multifaceted functions, and intricate signaling pathways orchestrated by c-MET across cancer types. Furthermore, we highlight the pivotal role of c-MET-targeted therapies in breast cancer, offering a clinical perspective on this promising avenue of intervention. In this pursuit, we strive to unravel the potential of c-MET as a beacon of hope in the fight against breast cancer, unveiling new horizons for therapeutic innovation. • Lack of FDA-approved c-MET inhibitors for breast cancer leaves a crucial treatment gap amidst its role in therapy resistance. • c-MET and HGF structural insights highlight intervention points and alternative splicing's impact. • Unraveling complexities in site-specific phosphorylation's impact on c-MET functions. • Diverse pathways, glycosylation, and noncanonical signaling govern c-MET's activity and degradation. • Onartuzumab, foretinib, tivantinib, cabozantinib, and capmatinib trials underscore breast cancer patient stratification needs. [ABSTRACT FROM AUTHOR]