Thromboembolic events in patients treated with anti-angiogenic drugs

Patrizia Ferroni, Vincenzo Formica, Mario Roselli, Fiorella Guadagni

Research output: Contribution to journalArticle

Abstract

Induction of neo-angiogenesis is a fundamental step in many pathological conditions. The therapeutic value of inhibiting angiogenesis is an interesting area of research in oncology, with vascular endothelial growth factor (VEGF) being the most suitable anti-angiogenic target. In the last decade a number of anti-VEGF drugs have demonstrated, especially in combination with standard chemotherapy, clinical efficacy in the treatment of different solid tumor types. As data from clinical trials on anti-VEGF drugs are becoming available, it is increasingly recognized that VEGF, in addition to being a permeability, proliferation, and migration factor, is also a maintenance and protection factor for endothelial cells, being capable of regulating multiple biological functions, i.e. the production of vasoactive mediators and the expression of components of the thrombolytic and coagulation pathways. Consequently, the disturbance of vascular homeostasis by blocking VEGF may lead to endothelial dysfunction and adverse vascular effects, such as venous and arterial thromboembolic events. In preclinical models angiogenesis and the increased expression of VEGF has been associated to altered expression of proinflammatory genes. These genes may be regulated in a biphasic manner, and it is possible that anti-VEGF therapy may disrupt a negative feedback loop that leads to potential in situ thrombus formation. Accordingly, combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was recently associated with an increased risk of thromboembolism. The present review considers the biological mechanisms and clinical impact of thromboembolic complications during anti-angiogenic treatments in cancer patients.

Original languageEnglish
Pages (from-to)102-113
Number of pages12
JournalCurrent Vascular Pharmacology
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Keywords

  • Bevacizumab
  • Endothelial dysfunction
  • Haemostatic activation
  • Nitric oxide
  • Oxidant stress
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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