Inhibition of HGF/MET as therapy for malignancy.
BACKGROUND
Inhibition of inappropriate tyrosine kinase activity by neoplasms is an attractive strategy for the treatment of malignancy.


OBJECTIVE
We aimed to produce a concise review of the potential role of hepatocyte growth factor (HGF)/Mesenchymal-epithelial transition factor (MET) tyrosine kinase pathway inhibition in the treatment of cancer.


METHODS
The current literature, abstracts and internet resources related to HGF/MET structure, function and inhibition are summarized. The potential of inhibiting this pathway as a therapy for cancer and remaining hurdles prior to routine clinical use of MET inhibition are discussed.


CONCLUSIONS
Current knowledge suggests that the inhibition of the HGF/MET pathway has significant potential for the treatment of cancer. A number of MET inhibitor molecules are nearing completion of their development for clinical use.
Naran
Sanjay
S
University of Pittsburgh School of Medicine, Division of Surgical Oncology, Department of Surgery, Pittsburgh, PA 15261, USA.
Zhang
Xinglu
X
Hughes
Steven J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016227:Benzoquinones / Q000008:administration & dosage / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met; D016337:RNA, Catalytic / Q000008:administration & dosage / Q000627:therapeutic use; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016227:Benzoquinones; C066855:HGF protein, human; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C001277:geldanamycin