J Cancer 2016; 7(6):633-649. doi:10.7150/jca.12663


Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

Witthawat Ariyawutyakorn1,3, Siriwimon Saichaemchan2,3, Marileila Varella-Garcia3✉

1. Faculty of Medicine, Chiang Mai University, 110 Intavarorod Rd., Muang, Chiang Mai, Thailand 50200.
2. Division of Oncology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, 315 Phayathai Rd., Ratchathewi, Bangkok, Thailand 10400.
3. Department of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Ave, RC1 South, L18-8118, Mail Stop 8117, Aurora, Colorado, USA 80045.

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Ariyawutyakorn W, Saichaemchan S, Varella-Garcia M. Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?. J Cancer 2016; 7(6):633-649. doi:10.7150/jca.12663. Available from http://www.jcancer.org/v07p0633.htm

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The MET signaling pathway plays an important role in normal physiology and its deregulation has proved critical for development of numerous solid tumors. Different technologies have been used to investigate the genomic and proteomic status of MET in cancer patients and its association with disease prognosis. Moreover, with the development of targeted therapeutic drugs, there is an urgent need to identify potential biomarkers for selection of patients who are more likely to derive benefit from these agents. Unfortunately, the variety of technical platforms and analysis criteria for diagnosis has brought confusion to the field and a lack of agreement in the evaluation of MET status as a prognostic or predictive marker for targeted therapy agents. We review the molecular mechanisms involved in the deregulation of the MET signaling pathway in solid tumors, the different technologies used for diagnosis, and the main factors that affect the outcome, emphasizing the urge for completing analytical and clinical validation of these tests. We also review the current clinical studies with MET targeted agents, which mostly focus on lung cancer.

Keywords: MET, HGF, FISH, IHC, molecular testing, targeted therapy.