Insights into platinum-induced peripheral neuropathy–current perspective

作     者：Andrijana Lazić Jelena Popović Tatjana Paunesku Gayle EWoloschak Milena Stevanović Andrijana Lazi?;Jelena Popovi?;Tatjana Paunesku;Gayle E.Woloschak;Milena Stevanovi?

作者机构：Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeBelgradeSerbia Feinberg School of MedicineDepartment of Radiation OncologyNorthwestern UniversityChicagoILUSA Faculty of BiologyUniversity of BelgradeBelgradeSerbia Serbian Academy of Sciences and ArtsBelgradeSerbia 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第9期

页      面：1623-1630页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by grant from the Ministry of Education,Science and Technological Development,Republic of Serbia(173051) supported by a UICC Yamagiwa-Yoshida Memorial International Cancer Study Grant(YY2/2015/381414) 

主　　题：chemotherapy-induced peripheral neuropathy CIPN DNA-Pt adducts dorsal root ganglia DRG model systems molecular mechanisms neurotoxic platinum based chemotherapy Pt sensory neurons treatment side effects 

摘      要：Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of platinum-based chemotherapy agents. This cluster of complications is often so debilitating that patients occasionally have to discontinue the therapy. Sensory neurons of dorsal root ganglia are at the core of chemotherapy-induced peripheral neuropathy symptoms. In these postmitotic cells, DNA damage caused by platinum chemotherapy interferes with normal functioning. Accumulation of DNA-platinum adducts correlates with neurotoxic severity and development of sensation of pain. While biochemistry of DNA-platinum adducts is the same in all cell types, molecular mechanisms affected by DNA-platinum adducts are different in cancer cells and non-dividing cells. This review aims to raise awareness about platinum associated chemotherapy-induced peripheral neuropathy as a medical problem that has remained unexplained for decades. We emphasize the complexity of this condition both from clinical and mechanistical point of view and focus on recent findings about chemotherapy-induced peripheral neuropathy in in vitro and in vivo model systems. Finally, we summarize current perspectives about clinical approaches for chemotherapy-induced peripheral neuropathy treatment.