[Angiogenesis inhibitors: mechanism of action and nephrotoxicity]

Abstract

Tumoral angiogenesis is a key mechanism involved in the growth and spread of cancer cells. The development of angiogenesis inhibitors, particularly those targeting the Vascular Endothelial Growth Factor (VEGF) pathway, has improved the prognosis and survival of many cancer patients since they were approved in 2005 in France. Vascular Endothelial Growth Factor inhibitors have different mechanisms of action, targeting either the ligand (e.g. bevacizumab, anti-Vascular Endothelial Growth Factor monoclonal antibody; aflibercept, recombinant anti-Vascular Endothelial Growth Factor fusion protein), or its receptors such as tyrosine kinase inhibitors (e.g. sunitinib or sorafenib). These treatments can be combined with conventional chemotherapy, or other anti-cancer therapies, and are associated with variable tolerance depending on the patient's clinical condition and comorbidities. Additionally, angiogenesis inhibition may be associated with cardiovascular and/or kidney toxicity and therefore special monitoring is needed during the treatment duration. Development of hypertension and proteinuria are the commonest renal side effects; these are generally manageable and reversible when treatment is stopped. However, more severe toxicities have been reported such as acute kidney injury, glomerular and/or vascular insults such as thrombotic microangiopathy, and more rarely tubulointerstitial damage. The prescribing physician should be aware of these potentially serious. This article describes the mechanisms of action of antiangiogenic agents and their potential toxicities, with particular respect to the kidneys.

Keywords: Anti-Vascular Endothelial Growth Factor; Hypertension; Microangiopathie thrombotique; Nephrotoxicity; Néphrotoxicité; Proteinuria; Protéinurie; Thrombotic microangiopathy; Vascular Endothelial Growth Factor targeted therapies.