VEGF signaling in cancer treatment.
Induction of angiogenesis represents one of the major hallmarks of cancer. The growth of new vessels is crucial to provide malignant cells with an adequate supply of oxygen and nutrients. It is generally accepted that vascular endothelial growth factor (VEGF) is a major driver of the angiogenic process in physiological and pathological processes in both embryo and adult. VEGF is often found overexpressed in tumors, as well as its receptors VEGFR1 and VEGFR2. Hence, several different strategies have been designed to target VEGF signal transduction. In the last decades, multiple inhibitors have been therapeutically validated in preclinical models and several clinical trials. Neutralizing monoclonal antibodies against VEGF and small molecule tyrosine kinase inhibitors targeting VEGFRs have been shown to block its angiogenic activity, resulting in tumor vascular regression, anti-tumor effects and improvements in patient survival. However, side effects and lack of efficacy in some instances challenge the potential clinical impact of these therapies. This review examines the role of VEGF signaling in cancer and outlines the current status of anti-angiogenic therapies against VEGF pathway.
Daniela
D
Sia
Clara
C
Alsinet
Pippa
P
Newell
HCC Translational Research Laboratory, BCLC Group, Liver Unit, CIBERehd, Hospital Clinic, IDIBAPS, Rossello 153, 08036 Barcelona, Spain. augusto.villanueva@ciberehd.org.
Augusto
A
Villanueva
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2