MET exon 14 juxtamembrane splicing mutations: clinical and therapeutical perspectives for cancer therapy

摘要: The MET proto-oncogene plays crucial roles in cell growth and proliferation, survival apoptosis, epithelial-mesenchymal transition (EMT) invasion, potentially conditioning the development progression of carcinogenesis process. MET-associated aberrant signaling could be triggered by a variety mechanisms, such as mutations, gene amplification, increased copy number Met/HGF protein expression. Among various alterations, exon 14 splicing abnormalities, causing loss Met juxtamembrane (JM) domain, recently emerged new potential oncogenic driver have been identified validated across different cancer histology subtypes. Moreover, this aberration was found to mutually exclusive with other recognized drivers, thus strongly nominating its role. Recently, clinical activity anti-Met-targeted therapy demonstrated particularly patients harboring skipping lung cancer, resulting renewed enthusiasm further test precision prospective trials. In review, key preclinical data regarding variants an actionable genomic are described, perspectives deriving from validation alteration target, which may allow driving therapeutic approach molecularly selected patients' subgroup, explored.