Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy

Nat Rev Cancer. 2018 Jun;18(6):341-358. doi: 10.1038/s41568-018-0002-y.


The MET oncogene encodes an unconventional receptor tyrosine kinase with pleiotropic functions: it initiates and sustains neoplastic transformation when genetically altered ('oncogene addiction') and fosters cancer cell survival and tumour dissemination when transcriptionally activated in the context of an adaptive response to adverse microenvironmental conditions ('oncogene expedience'). Moreover, MET is an intrinsic modulator of the self-renewal and clonogenic ability of cancer stem cells ('oncogene inherence'). Here, we provide the latest findings on MET function in cancer by focusing on newly identified genetic abnormalities in tumour cells and recently described non-mutational MET activities in stromal cells and cancer stem cells. We discuss how MET drives cancer clonal evolution and progression towards metastasis, both ab initio and under therapeutic pressure. We then elaborate on the use of MET inhibitors in the clinic with a critical appraisal of failures and successes. Ultimately, we advocate a rationale to improve the outcome of anti-MET therapies on the basis of thorough consideration of the entire spectrum of MET-mediated biological responses, which implicates adequate patient stratification, meaningful biomarkers and appropriate clinical end points.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Survival / genetics
  • Clonal Evolution / genetics*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplastic Stem Cells / metabolism*
  • Oncogene Addiction / genetics
  • Oncogenes
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Stromal Cells / metabolism


  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-met