301. Known and novel roles of the METoncogene in cancer: a coherent approach to targeted therapy
- Author
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Comoglio, Paolo, Trusolino, Livio, and Boccaccio, Carla
- Abstract
The METoncogene 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. The METoncogene encodes a receptor tyrosine kinase with pleiotropic functions. In this Review, Comoglio et al. describe the known and novel MET-mediated biological responses in cancer and discuss how clinical trials testing anti-MET therapies should be designed with careful consideration of these oncogenic functions of MET.
- Published
- 2018
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