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预防抗癌治疗引起的神经毒性:从 DNA 损伤角度看问题。

Prevention of anticancer therapy-induced neurotoxicity: Putting DNA damage in perspective.

机构信息

Institute of Toxicology, Medical Faculty, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany.

出版信息

Neurotoxicology. 2022 Jul;91:1-10. doi: 10.1016/j.neuro.2022.04.009. Epub 2022 Apr 26.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side effect of conventional anticancer therapeutics (cAT) that significantly impacts the quality of life of tumor patients. The molecular mechanisms of CIPN are incompletely understood and there are no effective preventive or therapeutic measures available to date. Here, we present a brief overview of the current knowledge about mechanisms underlying CIPN and discuss DNA damage-related stress responses as feasible targets for the prevention of CIPN. In addition, we discuss that the nematode Caenorhabditis elegans is a useful 3R-conform model organism to further elucidate molecular mechanisms of CIPN and to identify novel lead compounds protecting from cAT-triggered neuropathy.

摘要

化疗引起的周围神经病(CIPN)是传统抗癌疗法(cAT)的一种严重副作用,严重影响肿瘤患者的生活质量。CIPN 的分子机制尚不完全清楚,迄今为止尚无有效的预防或治疗措施。在这里,我们简要概述了目前关于 CIPN 潜在机制的知识,并讨论了与 DNA 损伤相关的应激反应作为预防 CIPN 的可行靶点。此外,我们还讨论了秀丽隐杆线虫是一种有用的 3R 一致性模式生物,可进一步阐明 CIPN 的分子机制,并确定新型先导化合物以预防 cAT 引发的神经病。

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