Columbia University, Zuckerman Mind Brain and Behavior Institute, Jerome L. Greene Science Center, 3227 Broadway, L9-005, New York, NY 10027, USA.
Exp Neurol. 2023 Jan;359:114258. doi: 10.1016/j.expneurol.2022.114258. Epub 2022 Oct 21.
Paclitaxel is a common chemotherapeutic agent widely used to treat solid cancer. However, it frequently causes peripheral sensory neuropathy, resulting in sensory abnormalities and pain in patients receiving treatment for cancer. As one of the most widely used chemotherapeutics, many preclinical studies on paclitaxel-induced peripheral neuropathy (PIPN) have been performed. Yet, there remain no effective options for treatment or prevention. Due to paclitaxel's ability to bind to and stabilize microtubules, a change in microtubule dynamics and subsequent disruptions in axonal transport has been predicted as a major underlying cause of paclitaxel-induced toxicity. However, the systemic understanding of PIPN mechanisms is largely incomplete, and various phenotypes have not been directly attributed to microtubule-related effects. This review aims to provide an overview of the literature involving paclitaxel-induced alteration in microtubule dynamics, axonal transport, and endocytic changes. It also aims to provide insights into how the microtubule-mediated hypothesis may relate to various phenotypes reported in PIPN studies.
紫杉醇是一种常用的化疗药物，广泛用于治疗实体瘤。然而，它经常引起周围感觉神经病变，导致接受癌症治疗的患者出现感觉异常和疼痛。作为最广泛使用的化疗药物之一，已经进行了许多紫杉醇诱导的周围神经病变 (PIPN) 的临床前研究。然而，目前仍没有有效的治疗或预防方法。由于紫杉醇能够与微管结合并稳定微管，因此预测微管动力学的改变以及随后的轴突运输中断是紫杉醇诱导毒性的主要潜在原因。然而，对 PIPN 机制的系统认识在很大程度上仍不完整，并且各种表型尚未直接归因于与微管相关的影响。本综述旨在概述涉及紫杉醇诱导的微管动力学、轴突运输和内吞变化的文献。它还旨在探讨微管介导的假说如何与 PIPN 研究中报告的各种表型相关。
