Cardiovascular and renal toxicity during angiogenesis inhibition: clinical and mechanistic aspects.
Inhibition of angiogenesis with humanized monoclonal antibodies to vascular endothelial growth factor (VEGF) or with tyrosine kinase inhibitors targeting VEGF receptors has become an established treatment for various tumor types. Contrary to expectations, angiogenesis inhibition by blocking VEGF-mediated signaling is associated with serious side effects including hypertension and renal and cardiac toxicity in a substantial proportion of patients. Fortunately, most of these side effects as discussed in this paper seem to be manageable, but likely become more problematic when survival increases. Although several hypotheses regarding the etiology of angiogenesis inhibition-related cardiovascular and renal side effects have been postulated, many of the underlying pathophysiological mechanisms remain to be elucidated. This may lead to the development of more specific angiogenesis inhibitors, better management of their side effects and may potentially provide new insights into the pathogenesis of cardiovascular disease in general.
Kappers
Mariëtte Hw
MH
Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
van Esch
Joep H M
JH
Sleijfer
Stefan
S
Danser
A H Jan
AH
van den Meiracker
Anton H
AH
D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor