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The multiple paths towards MET receptor addiction in cancer

Oncogene volume 37, pages 3200–3215 (2018)Cite this article

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Abstract

Targeted therapies against receptor tyrosine kinases (RTKs) are currently used with success on a small proportion of patients displaying clear oncogene activation. Lung cancers with a mutated EGFR provide a good illustration. The efficacy of targeted treatments relies on oncogene addiction, a situation in which the growth or survival of the cancer cells depends on a single deregulated oncogene. MET, a member of the RTK family, is a promising target because it displays many deregulations in a broad panel of cancers. Although clinical trials having evaluated MET inhibitors in large populations have yielded disappointing results, many recent case reports suggest that MET inhibition may be effective in a subset of patients with unambiguous MET activation and thus, most probably, oncogene addiction. Interestingly, preclinical studies have revealed a particularity of MET addiction: it can arise through several mechanisms, and the mechanism involved can differ according to the cancer type. The present review describes the different mechanisms of MET addiction and their consequences for diagnosis and therapeutic strategies. Although in each cancer type MET addiction affects a restricted number of patients, pooling of these patients across all cancer types yields a targetable population liable to benefit from addiction-targeting therapies.

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Acknowledgements

This work was supported by the CNRS, the Institut Pasteur de Lille, and INSERM, and by grants from the ‘Ligue contre le Cancer, comité Nord’, the ‘Association pour la Recherche sur le Cancer’, the ‘Institut National du Cancer’, the ‘Cancéropôle Nord-Ouest’ and the ‘Site de Recherche Intégrée sur le Cancer, SIRIC ONCOLille’.

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Authors and Affiliations

  1. Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies, F-59000, Lille, France

    Leslie Duplaquet, Zoulika Kherrouche, Simon Baldacci, Philippe Jamme, Alexis B. Cortot, Marie-Christine Copin & David Tulasne

  2. Thoracic Oncology Department, Univ. Lille, CHU Lille, F-59000, Lille, France

    Alexis B. Cortot

  3. Univ. Lille, Institut de Pathologie, Avenue Oscar Lambret, CHU Lille, F-59000, Lille, France

    Marie-Christine Copin

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  1. Leslie Duplaquet
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Duplaquet, L., Kherrouche, Z., Baldacci, S. et al. The multiple paths towards MET receptor addiction in cancer. Oncogene 37, 3200–3215 (2018). https://doi.org/10.1038/s41388-018-0185-4

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