title: The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer.
abstract: Survival rates for ovarian cancer have remained relatively stable for the past 2 decades despite advances in surgical techniques and cytotoxic chemotherapeutics, indicating a requirement for better therapies. One pathway currently proposed for targeting is the HGF/cMET pathway. Upregulated in a number of tumour types, cMET is a tyrosine kinase receptor expressed on epithelial cells. In ovarian cancer, it has been identified as highly expressed in the four major subtypes, with expression estimates ranging from 11 to 68 % of cases. HGF, the only known ligand for cMET, is found at high levels in both serum and ascites in women with ovarian cancer, and is proposed to induce both migration and metastasis. However, clinically validated biomarkers are not yet available for either HGF or cMET, preventing a clear understanding of the true rate of overexpression, or its correlation with prognosis. Despite this, a number of agents against HGF and cMET are currently being investigated in clinical trials for multiple tumour types, including ovarian. However, a lack of patient selection, biomarker usage, and post hoc analysis correlating response with expression has resulted in the majority of these trials showing little beneficial effect from these agents, indicating that additional research is required to determine their usefulness in patients with ovarian cancer.
authors.affiliation: Wolfson Wohl Cancer Research Centre, University of Glasgow, Switchback Rd, Glasgow, G61 1QH, UK. Kim.Moran-Jones@Glasgow.ac.uk.|The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 370 Victoria St, Sydney, NSW, 2010, Australia. Kim.Moran-Jones@Glasgow.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Moran-Jones
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D000077216:Carcinoma, Ovarian Epithelial; D002869:Chromosome Aberrations; D002986:Clinical Trials as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met