Renal side effects of VEGF-blocking therapy

Abstract

Neoangiogenesis is a necessary key event for tumourgrowth and metastatic dissemination. Vascular endothelialgrowth factor (VEGF) is produced by various tumours of acertain size to supply the cancer with new blood vessels.Production of VEGF is related to aggressiveness, meta-static potential and relapse of tumours [1]. Thus, anti-VEGF therapies that either block the extracellular bindingof VEGF to its receptor (anti-VEGF antibodies) or inhibitintracellular signalling pathways of VEGF receptors (re-ceptor tyrosine kinase inhibitors) have become an innova-tive target in the treatment of cancers. Bevacizumab is ahumanized monoclonal antibody directed against VEGF-A. It is used as first-line treatment for patients with meta-static colorectal carcinoma [2]. Sunitinib (Sutent) is aVEGFR-2/-3 tyrosine kinase inhibitor approved by theFood and Drug Administration for the treatment of gastro-intestinal stromal tumours and as first-line treatment forpatients with metastatic renal cell cancer [3]. Even thoughanti-VEGF therapies are generally well tolerated, bleeding,hypertension and asymptomatic proteinuria are well-known side effects. Renal damage which is infrequentlyreported as proteinuria is usually reversible, but in somerare cases nephrotic-range proteinuria, acute renal dys-function, interstitial nephritis and thrombotic microangio-pathy were reported [4,5].