靶向自噬在阿霉素诱导的心脏毒性:科学景观和治疗创新的综合综述

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Shiqi Wang , Lu Wang , Hongxin Cheng , Hanbin Li , Qing Zhang , Chengqi He , Chenying Fu , Quan Wei
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引用次数: 0

摘要

多柔比星(DOX)诱导的心脏毒性(DIC)对老年癌症患者构成重大威胁,常导致严重的心功能障碍并使癌症治疗结果复杂化。自噬是DIC的核心机制之一,被认为是关键的治疗靶点。我们通过文献计量学方法分析了DIC自噬领域的研究现状。共查明并列入了与本专题有关的292份出版物。在此基础上,结合已收录的老年医学文献和相关研究,总结了衰老心脏和DIC自噬的特点、针对自噬的治疗策略以及临床翻译中面临的挑战。我们的综述表明,该领域的研究热点集中在如何平衡癌症治疗效果与心脏毒性之间的关系,前沿则集中在通过自噬调节探索新的治疗策略。衰老心脏的自噬能力明显降低,加速心肌纤维化、收缩功能障碍、慢性炎症的发生。自噬对DIC具有显著的双向调节作用。此外,自噬的动态调节受DOX剂量梯度、暴露时间窗、实验模型和给药方法差异的显著影响。dexrazoxane和褪黑素等药物以及有氧训练和阻力训练等康复疗法可以调节心肌细胞自噬,并具有临床转化潜力。然而,现有临床研究中的年龄异质性破坏了研究结果对老年癌症患者的普遍性。未来的治疗优化需要基于老年人特定器官功能衰退模式的方案定制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting autophagy in doxorubicin-induced cardiotoxicity: A comprehensive review of scientific landscapes and therapeutic innovations
Doxorubicin (DOX)-induced cardiotoxicity (DIC) poses a major threat to elderly cancer patients, often leading to severe cardiac dysfunction and complicating the outcome of cancer treatment. Autophagy is one of the core mechanisms of DIC and is considered a key therapeutic target. We analyzed the status of research in the field of autophagy in DIC via bibliometric methods. A total of 292 publications related to this topic were identified and included. Furthermore, based on included publications and relevant studies in the field of geriatrics, the characteristics of autophagy in the aging heart and DIC, therapeutic strategies targeting autophagy, and challenges in clinical translation were summarized. Our review reveals that research hotspots in the field focus on how to balance the relationship between the effects of cancer treatment and cardiotoxicity, and the frontiers focus on exploring new therapeutic strategies via autophagy regulation. The autophagy ability of aging hearts is significantly reduced, which accelerates the occurrence of myocardial fibrosis, systolic dysfunction, and chronic inflammation. Autophagy has significant bidirectional regulatory effects on DIC. Additionally, the dynamic regulation of autophagy is significantly affected by dose gradients of DOX, exposure time windows, experimental models, and differences in administration methods. Drugs such as dexrazoxane and melatonin, as well as rehabilitation therapies such as aerobic training and resistance training, can regulate cardiomyocyte autophagy and have clinical translational potential. However, age heterogeneity in existing clinical studies undermines the generalizability of findings to elderly cancer patients. Future therapeutic optimization requires regimen customization based on elderly specific organ function decline patterns.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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