title: Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge.
abstract: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007, India. wasia.rizwani@gmail.com.
authors.forename: Wasia
authors.initials: W
authors.lastname: Rizwani
authors.affiliation: Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610, USA. amanda.allen@ufl.edu.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Allen
authors.affiliation: Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610, USA. Jose.Trevino@surgery.ufl.edu.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Trevino
keywords: HGF; acidosis; chemotherapy; desmoplasia; hypoxia; pancreatic cancer