title: VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs.
abstract: Systemic administration of antiangiogenic drugs that target components of the vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway has become a viable therapeutic option for patients with various types of cancer. Nevertheless, these drugs can drive alterations in healthy vasculatures, which in turn are associated with adverse effects in healthy tissues. VEGF is crucial for vascular homeostasis and the maintenance of vascular integrity and architecture in endocrine organs. Given these critical physiological functions, systemic delivery of drugs that target VEGF signalling can block VEGF-mediated vascular functions in endocrine organs, such as the thyroid gland, and lead to endocrine dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin sensitivity. This Review discusses emerging evidence from preclinical and clinical studies that contributes to understanding the mechanisms that underlie the vascular changes and subsequent modulations of endocrine function that are induced by targeted inhibition of VEGF signalling. Understanding these mechanisms is crucial for the design of antiangiogenic drugs with minimal associated adverse effects that will enable effective treatment of patients with cancer.
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Nobels vag 16, 17177 Stockholm, Sweden.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D004703:Endocrine System / Q000098:blood supply; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor