Interaction between Regulated Cell Death Pathways and Core Cellular Processes: Unraveling the Molecular Mechanisms of Cardiotoxicity of Antitumor Drugs.

With improved cancer survival, cancer therapy-related cardiovascular toxicity has emerged as a major non-cancer cause of morbidity and mortality in cancer survivors. The marked heterogeneity of CTR-CVT cannot be fully explained by single-pathway models, underscoring the need for a systems-level framework centered on regulated cell death networks. This review integrates recent advances to propose an RCD-cellular process interaction network in CTR-CVT, focusing on apoptosis, ferroptosis, pyroptosis, necroptosis, and selected emerging RCD modalities. We emphasize the mitochondrial dynamics-autophagic flux-metabolic reprogramming axis as a central regulatory module that shapes RCD activation, pathway crosstalk, and cell fate under anticancer drug stress. We also incorporate the reverse cardio-oncology concept to discuss potential bidirectional interactions between myocardial injury and tumor progression, and to identify therapeutic targets that enable cardioprotection while preserving antitumor efficacy. Building on this framework, we outline a translational strategy that integrates mechanism-based risk stratification, biomarker-guided early warning, and targeted cardioprotection, with reference to the 2022 ESC Cardio-Oncology Guidelines and representative clinical scenarios including breast cancer, hematological malignancies, and lung cancer. This mechanism-oriented approach may support biomarker discovery, mechanism-matched intervention, and the development of precision cardio-oncology. Future studies should prioritize mitochondrial quality control and metabolic plasticity as therapeutic entry points to reduce cardiovascular risk without compromising cancer treatment outcomes.