Meng Chenchen, Wang Yali, Zheng Tiantian, Rong Zheng, Lv Zhengtian, Wu Chenxia, Zhou Xinbin, Mao Wei
The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
Department of Cardiology, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China.
Chem Biol Interact. 2025 Feb 1;407:111379. doi: 10.1016/j.cbi.2025.111379. Epub 2025 Jan 8.
As a fundamental component of antitumor therapy, chemotherapy-induced cardiotoxicity (CIC) has emerged as a leading cause of long-term mortality in patients with malignant tumors. Unfortunately, there are currently no effective therapeutic preventive or treatment strategies, and the underlying pathophysiological mechanisms of CIC remain inadequately understood. A growing number of studies have shown that different mechanisms of cell death, such as apoptosis, pyroptosis, and necroptosis, are essential for facilitating the cardiotoxic effects of chemotherapy. The PANoptosis mode represents a highly synchronized and dynamically balanced programmed cell death (PCD) process that integrates the principal molecular characteristics of necroptosis, apoptosis, and pyroptosis. Recent research has revealed a significant correlation between PANoptosis and the apoptosis of tumor cells. Chemotherapy drugs can activate PANoptosis, which is involved in the development of cardiovascular diseases. These findings suggest that PANoptosis marks the point where the effectiveness of chemotherapy against tumors overlaps with the onset and development of cardiovascular diseases. Furthermore, previous studies have demonstrated that CIC can simultaneously induce pyrodeath, apoptosis, and necrotic apoptosis. Therefore, PANoptosis may represent a potential mechanism and target for the prevention of CIC. This study explored the interactions among the three main mechanisms of PCD, pyroptosis, apoptosis, and necroptosis in CICs and analyzed the relevant literature on PANoptosis and CICs. The purpose of this work is to serve as a reference for future investigations on the role of PANoptosis in the development and mitigation of cardiotoxicity associated with chemotherapy.
作为抗肿瘤治疗的基本组成部分，化疗诱导的心脏毒性（CIC）已成为恶性肿瘤患者长期死亡的主要原因。不幸的是，目前尚无有效的治疗性预防或治疗策略，CIC的潜在病理生理机制仍未得到充分了解。越来越多的研究表明，不同的细胞死亡机制，如凋亡、焦亡和坏死性凋亡，对于促进化疗的心脏毒性作用至关重要。泛凋亡模式代表了一种高度同步且动态平衡的程序性细胞死亡（PCD）过程，它整合了坏死性凋亡、凋亡和焦亡的主要分子特征。最近的研究揭示了泛凋亡与肿瘤细胞凋亡之间存在显著相关性。化疗药物可激活泛凋亡，其与心血管疾病的发生发展有关。这些发现表明，泛凋亡标志着化疗对肿瘤的有效性与心血管疾病的发生发展相互重叠的关键点。此外，先前的研究表明，CIC可同时诱导热死亡、凋亡和坏死性凋亡。因此，泛凋亡可能代表了预防CIC的潜在机制和靶点。本研究探讨了CIC中PCD的三种主要机制，即焦亡、凋亡和坏死性凋亡之间的相互作用，并分析了有关泛凋亡和CIC的相关文献。这项工作的目的是为未来关于泛凋亡在化疗相关心脏毒性的发生和减轻中的作用的研究提供参考。
