title: c-Met as a Target for Personalized Therapy.
abstract: MET and its ligand HGF are involved in many biological processes, both physiological and pathological, making this signaling pathway an attractive therapeutic target in oncology. Downstream signaling effects are transmitted via mitogen-activated protein kinase (MAPK), PI3K (phosphoinositide 3-kinase protein kinase B)/AKT, signal transducer and activator of transcription proteins (STAT), and nuclear factor-κB. The final output of the terminal effector components of these pathways is activation of cytoplasmic and nuclear processes leading to increases in cell proliferation, survival, mobilization and invasive capacity. In addition to its role as an oncogenic driver, increasing evidence implicates MET as a common mechanism of resistance to targeted therapies including EGFR and VEGFR inhibitors. In the present review, we summarize the current knowledge on the role of the HGF-MET signaling pathway in cancer and its therapeutic targeting (HGF activation inhibitors, HGF inhibitors, MET antagonists and selective/nonselective MET kinase inhibitors). Recent advances in understanding the role of this pathway in the resistance to current anticancer strategies used in lung, kidney and pancreatic cancer are discussed.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands. ; Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Garajová
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands. ; Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
keywords: HGF; MET; NSCLC; drug resistance; pancreatic cancer; renal cancer; targeted therapy