Title:Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Volume: 7
Issue: 3
Author(s): Jasmine Passerini, Adriana Romiti, Chiara D'Antonio, Vittoria Mastromarino, Paolo Marchetti, Massimo Volpe and Elena Conti
Affiliation:
Keywords:
Angiogenesis inhibitors, bevacizumab, cardiotoxicity, hypertension, IGF-1, myocardial infarction, tyrosinkinases,
VEGF, Tyrosinkinase, hypertension
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.
