Solomon Abhishikt David, Dabral Swarna, Brajesh Raman Gulab, Day Billy W, Juric Matea, Zielonka Jacek, Bosnjak Zeljko J, Pant Tarun
Adams School of Dentistry, Oral and Craniofacial Biomedicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India.
Int J Mol Sci. 2025 Apr 23;26(9):3966. doi: 10.3390/ijms26093966.
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.
化疗相关心脏毒性（CTRTOX）是一部分癌症患者接受癌症治疗时常见且严重的副作用。导致这些患者心脏严重毒性的潜在因素和相关机制尚不清楚。尽管获取人类受试者及其心室心肌细胞（CMs）仍面临挑战，但在过去几十年中，基于人类诱导多能干细胞（hiPSC）技术的CM分化方案取得的进展为基于iPSC的人类心脏病模型铺平了道路。在此，我们对CTRTOX的潜在机制进行详细分析。我们还将讨论不同动物模型和临床试验中治疗策略的最新进展。此外，我们探索基于iPSC的模型在识别新的功能靶点以及为癌症患者开发更安全的化疗方案方面的前景，这可能有助于开发个性化心脏保护剂及其在临床实践中的应用。
