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治疗癌症及相关治疗诱导性心脏毒性的靶向自噬调节策略进展

Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity.

作者信息

Ling Lauren A, Boukhalfa Asma, Kung Andrew H, Yang Vicky K, Chen Howard H

机构信息

Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington Street, #80, Boston, MA 02111, USA.

School of Medicine, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA.

出版信息

Pharmaceuticals (Basel). 2025 May 1;18(5):671. doi: 10.3390/ph18050671.

Abstract

Autophagy, an evolutionarily conserved process, plays an important role in cellular homeostasis and human diseases. Cardiovascular dysfunction, which presents during cancer treatment or in cancer-free individuals years after treatment, is a growing clinical challenge. Millions of cancer survivors and patients face an unpredictable risk of developing cardiotoxicity. Cardiotoxicity due to cancer treatment, as well as cancer progression, has been linked to autophagy dysregulation. Modulating autophagy has been further proposed as a therapeutic treatment for both cancer and cardiovascular disorders. The safe and effective use of autophagy modulation as a cardioprotective strategy during cancer treatment especially requires careful consideration and experimentation to minimize the impact on cancer treatment. We focus here on recent advances in targeted autophagy modulation strategies that utilize interdisciplinary approaches in biomedical sciences and are potentially translatable to treat cardiotoxicity and improve cancer treatment outcomes. This review highlights non-small molecule autophagy modulators to enhance targeted therapy, nanomedicine for autophagy modulation and monitoring, and in vitro models and future experiments needed to bring novel autophagy discoveries from basic research to clinical translation.

摘要

自噬是一个进化上保守的过程,在细胞内稳态和人类疾病中发挥着重要作用。心血管功能障碍在癌症治疗期间或治疗数年后的无癌个体中出现,是一个日益严峻的临床挑战。数以百万计的癌症幸存者和患者面临着发生心脏毒性的不可预测风险。癌症治疗以及癌症进展导致的心脏毒性与自噬失调有关。进一步提出调节自噬作为癌症和心血管疾病的一种治疗方法。在癌症治疗期间将自噬调节作为一种心脏保护策略安全有效地使用,尤其需要仔细考虑和试验,以尽量减少对癌症治疗的影响。我们在此关注靶向自噬调节策略的最新进展,这些策略利用生物医学科学中的跨学科方法,并且有可能转化为治疗心脏毒性和改善癌症治疗结果。这篇综述重点介绍了用于增强靶向治疗的非小分子自噬调节剂、用于自噬调节和监测的纳米医学,以及将自噬新发现从基础研究转化为临床应用所需的体外模型和未来实验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1227/12114528/f89a549b22ad/pharmaceuticals-18-00671-g001.jpg

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