Department of Radiation Oncology, Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2021 Feb 17;22(4):1975. doi: 10.3390/ijms22041975.
Platinum-based chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting effects of cancer treatment and results in dose reduction and discontinuation of life-saving chemotherapy. Its debilitating effects are often permanent and lead to lifelong impairment of quality of life in cancer patients. While the mechanisms underlying the toxicity are not yet fully defined, dorsal root ganglia sensory neurons play an integral role in symptom development. DNA-platinum adducts accumulate in these cells and inhibit normal cellular function. Nucleotide excision repair (NER) is integral to the repair of platinum adducts, and proteins involved in its mechanism serve as potential targets for future therapeutics. This review aims to highlight NER's role in cisplatin-induced peripheral neuropathy, summarize current clinical approaches to the toxicity, and discuss future perspectives for the prevention and treatment of CIPN.
铂类化疗引起的周围神经病（CIPN）是癌症治疗中最常见的剂量限制效应之一，导致剂量减少和挽救生命的化疗中断。其致残影响往往是永久性的，导致癌症患者的生活质量终生受损。虽然其毒性的机制尚未完全确定，但背根神经节感觉神经元在症状发展中起着重要作用。这些细胞中积累 DNA-铂加合物，抑制正常细胞功能。核苷酸切除修复（NER）是修复铂加合物的重要组成部分，其机制中涉及的蛋白质可作为未来治疗的潜在靶点。本文旨在强调 NER 在顺铂诱导的周围神经病中的作用，总结目前对这种毒性的临床处理方法，并讨论预防和治疗 CIPN 的未来展望。
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