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Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for
Abhishikt David Solomon1, Swarna Dabral2, Raman Gulab Brajesh3
1Adams School of Dentistry, Oral and Craniofacial Biomedicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Abstract:
Chemotherapy-related cardiotoxicity (CTRTOX) is a profound and common side effect of cancer-based therapy in a subset of patients. The underlying factors and the associated mechanisms contributing to severe toxicity of the heart among these patients remain unknown. While challenges remain in accessing human subjects and their ventricular cardiomyocytes (CMs), advancements in human induced pluripotent stem cell (hiPSC)-technology-based CM differentiation protocols over the past few decades have paved the path for iPSC-based models of human cardiac diseases. Here, we offer a detailed analysis of the underlying mechanisms of CTRTOX. We also discuss the recent advances in therapeutic strategies in different animal models and clinical trials. Furthermore, we explore the prospects of iPSC-based models for identifying novel functional targets and developing safer chemotherapy regimens for cancer patients that may be beneficial for developing personalized cardioprotectants and their application in clinical practice.
Insights
Chemotherapy-related cardiotoxicity mechanisms remain unclear. Human induced pluripotent stem cell (hiPSC)-based models offer new avenues for understanding and treating heart damage from cancer therapies.
Area of Science:
- Cardiology
- Oncology
- Stem Cell Biology
Background:
- Chemotherapy-related cardiotoxicity (CTRTOX) is a significant concern in cancer treatment, affecting a subset of patients.
- The precise mechanisms underlying CTRTOX and severe cardiac damage remain largely unknown.
- Accessing human cardiomyocytes for research is challenging, limiting direct study of CTRTOX.
Purpose of the Study:
- To provide a comprehensive analysis of the mechanisms driving chemotherapy-related cardiotoxicity.
- To review recent therapeutic advancements for CTRTOX in preclinical and clinical settings.
- To explore the potential of human induced pluripotent stem cell (hiPSC)-based models in CTRTOX research.
Main Methods:
- Analysis of existing literature on CTRTOX mechanisms and therapeutic strategies.
- Review of advancements in hiPSC technology for generating cardiomyocytes.
- Exploration of iPSC-based models for drug discovery and personalized medicine.
Main Results:
- Detailed examination of the molecular and cellular pathways involved in CTRTOX.
- Overview of current and emerging therapeutic interventions tested in animal models and human trials.
- Identification of iPSC-derived cardiomyocytes as a valuable tool for disease modeling.
Conclusions:
- hiPSC-based models hold significant promise for elucidating CTRTOX mechanisms.
- These models can aid in identifying novel therapeutic targets and developing safer chemotherapy regimens.
- Personalized cardioprotectants and improved clinical strategies may emerge from iPSC research.
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