An Observatory for the MET Oncogene: A Guide for Targeted Therapies

SIMPLE SUMMARY: The MET gene encodes a receptor critical for cell growth and repair. It plays diverse roles in processes like organ development, wound healing, and blood vessel formation. Genetic alterations in MET contribute to cancer progression, enabling tumor spread and resistance to treatment. Scientists are studying how to target MET to treat cancer. Despite progress, the complexity of MET’s functions in cancer challenges our understanding. This review explores recent discoveries about MET in cancer, its effects, potential therapies, and future directions. ABSTRACT: The MET proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role in cancer progression in a broad range of tumors; genetic/epigenetic alterations of MET drive tumor cell dissemination, metastasis, and acquired resistance to conventional and targeted therapies. Therefore, targeting MET emerged as a promising strategy, and many efforts were devoted to identifying the optimal way of hampering MET signaling. Despite encouraging results, however, the complexity of MET’s functions in oncogenesis yields intriguing observations, fostering a humbler stance on our comprehension. This review explores recent discoveries concerning MET alterations in cancer, elucidating their biological repercussions, discussing therapeutic avenues, and outlining future directions. By contextualizing the research question and articulating the study’s purpose, this work navigates MET biology’s intricacies in cancer, offering a comprehensive perspective.