Targeting the MET oncogene in cancer and metastases.
BACKGROUND
'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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Stella
Giulia M
GM
Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, I-10060 Candiolo, Turin, Italy. g.stella@smatteo.pv.it
Benvenuti
Silvia
S
Comoglio
Paolo M
PM
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009857:Oncogenes; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics*
D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met