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Updated: Jul 23, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Ferroptosis-induced Cardiotoxicity and Antitumor Drugs
1Molecular Pharmacology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133, Italy.
Abstract:
The induction of regulated cell death ferroptosis in tumors is emerging as an intriguing strategy for cancer treatment. Numerous antitumor drugs (e.g., doxorubicin, etoposide, tyrosine kinase inhibitors, trastuzumab, arsenic trioxide, 5-fluorouracil) induce ferroptosis. Although this mechanism of action is interesting for fighting tumors, the clinical use of drugs that induce ferroptosis is hampered by cardiotoxicity. Besides in cancer cells, ferroptosis induced by chemotherapeutics can occur in cardiomyocytes, and this feature represents an important drawback of antitumor therapy. This inconvenience has been tackled by developing less or no cardiotoxic antitumor drugs or by discovering cardioprotective agents (e.g., berberine, propofol, fisetin, salidroside, melatonin, epigallocatechin- 3gallate, resveratrol) to use in combination with conventional chemotherapeutics. This review briefly summarizes the molecular mechanisms of ferroptosis and describes the ferroptosis dependent mechanisms responsible for cardiac toxicity developed by cancer- suffering patients following the administration of some chemotherapeutics. Additionally, the pharmacological strategies very recently proposed for potentially preventing this inconvenience are considered.
Insights
Ferroptosis, a cell death pathway, shows promise for cancer treatment by inducing tumor cell death. However, chemotherapy-induced ferroptosis can harm heart cells, necessitating cardioprotective strategies.
Area of Science:
- Oncology
- Cardiology
- Molecular Biology
Background:
- Ferroptosis induction in tumors is a novel cancer treatment strategy.
- Many anticancer drugs trigger ferroptosis in cancer cells.
- Chemotherapy-induced ferroptosis can cause cardiotoxicity, a significant clinical challenge.
Purpose of the Study:
- To review ferroptosis mechanisms in cancer therapy.
- To describe ferroptosis-mediated cardiotoxicity from chemotherapeutics.
- To discuss emerging cardioprotective strategies against ferroptosis-induced cardiac damage.
Main Methods:
- Literature review of ferroptosis mechanisms.
- Analysis of chemotherapy-induced ferroptosis in cancer and cardiac cells.
- Evaluation of pharmacological cardioprotective interventions.
Main Results:
- Antitumor drugs like doxorubicin and 5-fluorouracil induce ferroptosis.
- Ferroptosis in cardiomyocytes is a key mechanism of chemotherapy-related cardiotoxicity.
- Cardioprotective agents (e.g., berberine, resveratrol) show potential in mitigating this toxicity.
Conclusions:
- Ferroptosis is a double-edged sword in cancer therapy, killing tumors but potentially harming the heart.
- Understanding ferroptosis-dependent cardiotoxicity is crucial for patient safety.
- Developing targeted cardioprotective strategies is essential for effective and safe cancer treatment.
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