Drug development of MET inhibitors: targeting oncogene addiction and expedience.
The MET tyrosine kinase stimulates cell scattering, invasion, protection from apoptosis and angiogenesis, thereby acting as a powerful expedient for cancer dissemination. MET can also be genetically selected for the long-term maintenance of the primary transformed phenotype, and some tumours appear to be dependent on (or 'addicted' to) sustained MET activity for their growth and survival. Because of its dual role as an adjuvant, pro-metastatic gene for some tumour types and as a necessary oncogene for others, MET is a versatile candidate for targeted therapeutic intervention. Here we discuss recent progress in the development of molecules that inhibit MET function and consider their application in a subset of human tumours that are potentially responsive to MET-targeted therapies.
Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin School of Medicine, Candiolo, Turin 10060, Italy. paolo.comoglio@ircc.it
Paolo M
PM
Comoglio
Silvia
S
Giordano
Livio
L
Trusolino
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D009857:Oncogenes; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met