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  • Review Article
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MET: a promising anticancer therapeutic target

Abstract

The MET pathway is dysregulated in many human cancers and promotes tumour growth, invasion and dissemination. Abnormalities in MET signalling have been reported to correlate with poor clinical outcomes and drug resistance in patients with cancer. Thus, MET has emerged as an attractive target for cancer therapy. Several MET inhibitors have been introduced into the clinic, and are currently in all phases of clinical trials. In general, initial results from these studies indicate only a modest benefit in unselected populations. In this Review, we discuss current challenges in developing MET inhibitors—including identification of predictive biomarkers—as well as the most-efficient ways to combine these drugs with other targeted agents or with classic chemotherapy or radiotherapy.

Key Points

  • Signalling through the receptor tyrosine kinase MET is dysregulated in cancer through multiple mechanisms: mutations, amplification and overexpression of MET and increased secretion of its ligand, hepatocyte growth factor (HGF)

  • A large number of antibodies and small molecules targeting various components of the MET signalling pathway have been introduced into the clinic

  • The monoclonal antibody against MET in patients with high expression is the most promising agent to date, as well as small-molecule inhibitors in tumours with mutated or amplified MET

  • Preclinical data showing how MET inhibitors overcome resistance to EGFR inhibitors have not been demonstrated in patients to date; early clinical trials have confirmed preclinical synergy between inhibitors of MET and angiogenesis

  • Currently there are no validated biomarkers to evaluate increased MET copy number, which leads to confusion in the literature about MET amplification and polysomy

  • Future and ongoing clinical trials will document the exact role of MET inhibitors in cancer therapy and refine predictive biomarkers

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Figure 1: Simplified schema of the MET signalling pathway.
Figure 2: Selected MET inhibitors and their inhibitory targets in the MET pathway.

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Peters, S., Adjei, A. MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol 9, 314–326 (2012). https://doi.org/10.1038/nrclinonc.2012.71

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