Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome

Jasmine      Passerini; Adriana      Romiti; Chiara      D'Antonio; Vittoria      Mastromarino; Paolo      Marchetti; Massimo      Volpe; Elena      Conti

doi:10.2174/157436212802481565

Abstract

Even though cancer therapies attain nowadays as many as 10 million survivors, some studies surprisingly report a higher risk of cardiovascular death compared with that of tumor recurrence. Cancer survivors are thus candidates for a thorough cardiovascular evaluation, because they acquire cardiovascular risk together with oncologic cure. VEGF or tyrosinkinase inhibitors, increasingly used in a large variety of tumours with a significant survival advantage, are prototypical drugs simultaneously realizing oncologic care and cardiotoxicity, by targeting angiogenic replicative pathways, involved in both cardiac health and cancer progression. The pathophysiology of cardiovascular disease, mainly consisting in defective angiogenesis, is indeed opposite to that of tumorigenesis and metastasis spreading, both crucially sustained by enhanced blood vessel development. The clinical expression of cardiotoxicity includes not only the development of a dilated hypokinetic cardiomyopathy, currently generally treated with cardiological drugs, but also hypertension, clinical or subclinical atherothrombotic ischemic heart disease and ischemic cardiomyopathy. These clinical syndromes deserve a more adequate cardiovascular assessment and appropriate advanced treatment strategies including percutaneous coronary intervention, coronary artery bypass graft, or device implantation. If not proactively suspected, diagnosed and treated, these manifestations may lead to cardiac events, and reduce overall survival.

This review analyzes the available evidence about molecular pathways, predictors and monitoring of impaired angiogenesis-driven cardiotoxicity. Even clinical relevance, pharmacodynamics and markers of efficacy of various intended or “accidental” antiangiogenic drugs will be discussed with the purpose of easing appropriate cardiological surveillance and treatment. Drug tailoring aimed at outcome and cost-effectiveness, according to both drug susceptibility and cardiovascular vulnerability will be finally revised.

Keywords: Angiogenesis inhibitors, bevacizumab, cardiotoxicity, hypertension, IGF-1, myocardial infarction, tyrosinkinases, VEGF, Tyrosinkinase, hypertension