title: Clinical advances in the development of novel VEGFR2 inhibitors.
abstract: Angiogenesis inhibitors have produced significant advances in the treatment of several tumors including colorectal, lung, ovarian and renal carcinomas. These agents, however, modestly impact on the overall cure rate, and their activity is often limited because of the early outbreak of redundant pathways or resistance mechanisms. Moreover, no clear predictive factor has been identified for treatment selection in the clinic. Preclinical evidence suggest that antibodies targeting the vascular endothelial growth factor (VEGF) axis may exert their activity throughout the inhibition of VEGF receptor 2 (VEGFR2) phosphorylation, a key factor in the cancer angiogenic process. Among other molecules, ramucirumab, an intravenously administered, fully humanized monoclonal antibody (mAb) targeting the extracellular domain of the receptor, and apatinib, a potent oral inhibitor of the intracellular domain, are emerging as original antiangiogenic opportunities. This up-to-date review focuses on the development of VEGFR2 inhibitors across multiple cancers and presents results of the most recent researches, ranging from early phase I studies to randomized phase III trials, in which those drugs have been tested as a single-agent or in combination with different chemotherapy regimens.
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fontanella
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ongaro
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolzonello
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Guardascione
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
keywords: Angiogenesis; antibodies anti-VEGFR2; apatinib; breast cancer; gastric cancer; lung cancer; ramucirumab; vascular endothelial growth factor receptor 2 (VEGFR2)