Medical Journal of Mashhad university of Medical Sciences

Medical Journal of Mashhad university of Medical Sciences

Molecular mechanisms of MET tyrosine kinase during tumor progression and metastasis

Document Type : Review article

Authors
Negin Taghehchian 1
Mohmmad Reza Abbaszadegan 2
Meysam Moghbeli 2
1 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
10.22038/mjms.2025.79037.4549
Abstract
Due to the side effects caused by common cancer treatments such as chemotherapy and radiotherapy, it is required to introduce the novel therapeutic options in cancer patients. In recent years, the molecular orientation of cancer treatment is considered as the most effective approach in personalized cancer medicine. The use of tyrosine kinase inhibitors can be a promising approach for cancer treatment. MET is a receptor tyrosine kinase that has a key role in inducing cell proliferation, angiogenesis, and cell migration, and tumor progression. MET deregulation is associated with poor prognosis and drug resistance in a wide range of cancers. Regarding the role of MET in many physiological and pathological processes, it can be considered as a therapeutic target in tumor cells. Small-molecule tyrosine kinase inhibitors (TKIs) such as crizotinib, capmatinib, and cabozantinib have reliable efficacy to improve progression-free survival in cancer patients by MET inhibition. Monoclonal antibodies also disrupt ligand-MET interactions to improve patient’s survival. However, resistance toward the MET inhibitors can be observed due to the various molecular mechanisms such as MET duplication and up regulation, mutation, and activation of parallel signaling pathways. PubMed, Google Scholar, Scopus, and Web of Science were used for data retrieval until 2024 using the “MET” and "cancer" keywords. This review has an important role to clarify the molecular biology of MET during tumor progression to introduce novel efficient therapeutic strategies to overcome resistance toward MET inhibitors among cancer patients.
Keywords
MET
Tyrosine kinase
Cancer
Drug resistance
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Medical Journal of Mashhad university of Medical Sciences
Volume 68, Issue 6
January and February 2026
Pages 1801-1814