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Updated: Nov 19, 2025
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Targeting endothelial cell metabolism for cardio-protection from the toxicity of antitumor agents
Lucia Morbidelli1, Sandra Donnini2, Marina Ziche2
1Department of Life Sciences, University of Siena, Via A. Moro 2, 53100, Siena, Italy. lucia.morbidelli@unisi.it.
Abstract:
The vascular endothelium plays a fundamental role in the maintenance of tissue homeostasis, regulating local blood flow and other physiological processes. Chemotherapeutic drugs and target therapies, including antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors, not only efficiently act against tumor growth, but may also induce endothelial dysfunction and cardiovascular toxicity. Continued research efforts aim to better understand, prevent and mitigate these chemotherapy associated cardiovascular diseases. Conventional chemotherapeutic agents, such as anthracyclines, platinum compounds, and taxanes, and newer targeted agents, such as bevacizumab, trastuzumab, and tyrosine kinase inhibitors, have known risk of cardiovascular toxicity, which can limit their effectiveness by promoting increased morbidity and/or mortality. This review describes a) the activity of anticancer agents in inducing endothelial dysfunction, b) the metabolic pathways and signalling cascades which may be targeted by protective agents able to maintain or restore endothelial cell function, such as endothelial nitric oxide synthase/fibroblast growth factor-2 (eNOS-FGF-2) pathway, and c) the drugs/strategies reported to improve endothelial function and to reduce the risks of cardiovascular diseases such as angiotensin converting enzyme inhibitors (ACEi) and beta blockers, that are fundamental therapies in chronic heart failure (HF), as well as non-standard HF treatments such ad nitric oxide donors and antioxidant strategies. There is increasing interest in whether ACEi, beta-blockers, and/or statins might prevent and/or therapeutically control cardiotoxic effects in cancer patients. Maintaining endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor drug-effectiveness, is essential for preserving or recovering cardiovascular homeostasis. In this respect, the early detection and immediate therapy of cardiovascular toxicity appear crucial for substantial recovery of cardiac function in cancer patients.
Insights
Cancer therapies can harm the heart by damaging the vascular endothelium. Research explores protective strategies, like targeting the eNOS-FGF-2 pathway and using heart failure drugs, to prevent cardiovascular toxicity during cancer treatment.
Area of Science:
- Cardiovascular Medicine
- Oncology
- Pharmacology
Background:
- The vascular endothelium is crucial for tissue homeostasis, regulating blood flow and physiological processes.
- Chemotherapeutic agents and targeted therapies, including antiangiogenic drugs, can induce endothelial dysfunction and cardiovascular toxicity, potentially limiting cancer treatment effectiveness.
- Cardiovascular diseases associated with chemotherapy pose significant risks, necessitating research into prevention and mitigation strategies.
Purpose of the Study:
- To review the mechanisms by which anticancer agents induce endothelial dysfunction.
- To identify metabolic pathways and signaling cascades, such as the endothelial nitric oxide synthase/fibroblast growth factor-2 (eNOS-FGF-2) pathway, that can be targeted for endothelial protection.
- To discuss drugs and strategies, including angiotensin converting enzyme inhibitors (ACEi), beta blockers, nitric oxide donors, and antioxidant strategies, for improving endothelial function and reducing cardiovascular risks in cancer patients.
Main Methods:
- Review of existing literature on anticancer agents and their cardiovascular effects.
- Analysis of pathways involved in endothelial dysfunction and potential therapeutic targets.
- Examination of pharmacological and non-pharmacological interventions for mitigating chemotherapy-induced cardiotoxicity.
Main Results:
- Anticancer agents like anthracyclines, platinum compounds, taxanes, bevacizumab, trastuzumab, and tyrosine kinase inhibitors are associated with known cardiovascular risks.
- The eNOS-FGF-2 pathway is highlighted as a potential target for maintaining or restoring endothelial cell function.
- ACEi, beta blockers, nitric oxide donors, and antioxidant strategies show promise in improving endothelial function and reducing cardiovascular risks.
Conclusions:
- Maintaining endothelial function during and after cancer treatment is essential for cardiovascular homeostasis without compromising anti-tumor efficacy.
- Early detection and prompt therapy of cardiovascular toxicity are critical for substantial cardiac function recovery in cancer patients.
- Further investigation into the role of ACEi, beta-blockers, and statins in preventing and managing cardiotoxicity in cancer patients is warranted.
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