Progress of antibody-based inhibitors of the HGF-cMET axis in cancer therapy.
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials. However, to date none of these HGF/cMET inhibitors have shown significant efficacy in clinical trials. Furthermore, no receptor tyrosine kinase inhibitors primarily targeting cMET have been approved. Given that neutralization of HGF or cMET does not cause significant adverse effects, inhibition of the HGF/cMET signaling pathway appears to be safe. In this review, we summarized the completed and ongoing clinical trials testing antibody- or protein-based anticancer drugs targeting cMET and HGF.
Cancer Research Institute, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.|Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.
Ki-Hyun
KH
Kim
Institute for Life Sciences, ASAN Medical Center, Songpa-gu, Seoul, Republic of Korea.
Hyori
H
Kim
D000818:Animals; D057134:Antibodies, Neutralizing / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D057134:Antibodies, Neutralizing; D000074322:Antineoplastic Agents, Immunological; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met