Targeting the MET oncogene in cancer and metastases

Abstract

Importance of the field: ‘Invasive growth’ is a genetic program involved in embryonic development and adult organ regeneration and usurped by cancer cells. Although its control is complex, tumor- and context-specific and regulated by several cytokines and growth factors, the role played by the MET oncogene is well documented. In human cancers the contribution of MET to invasive growth is mainly through overexpression, driven by unfavorable microenvironmental conditions. MET activation confers a selective advantage to neoplastic cells in tumor progression and drug resistance. A subset of tumors feature alterations of the MET gene and a consequent MET-addicted phenotype.

Areas covered in this review: The molecular basis and rationale of MET inhibition in cancer and metastases are discussed. A number of molecules designed to block MET signaling are under development and several Phase II trials are ongoing.

What the reader will gain: Knowledge of the state of the art of anti-MET targeted approaches and the molecular basis and strategies to select patients eligible for treatment with MET inhibitors.

Take home message: Due to its versatile functions MET is a promising candidate for cancer therapy. Understanding molecular mechanisms of sensitization and resistance to MET inhibitors is a priority to guide tailored therapies and select patients that are most likely to achieve a clinical benefit.

Keywords::

• gene amplification
• ligand antagonists
• neutralizing antibodies
• oncogene addiction
• small-molecule inhibitors
• somatic mutation

Notes

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