Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Mol Pain. 2017 Jan-Dec;13:1744806917714693. doi: 10.1177/1744806917714693.
Cancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the predominant complaints. CPIN not only decreases the quality of life of cancer survivors but also can lead to discontinuation of treatment, thereby adversely affecting survival. Consequently, minimizing the incidence or severity of CPIN is highly desirable, but strategies to prevent and/or treat CIPN have proven elusive. One difficulty in achieving this goal arises from the fact that the molecular and cellular mechanisms that produce CPIN are not fully known; however, one common mechanism appears to be changes in ion channel expression in primary afferent sensory neurons. The processes that underlie chemotherapy-induced changes in ion channel expression and function are poorly understood. Not all antineoplastic agents directly affect ion channel function, suggesting additional pathways may contribute to the development of CPIN Indeed, there are indications that these drugs may mediate their effects through cellular signaling pathways including second messengers and inflammatory cytokines. Here, we focus on ion channelopathies as causal mechanisms for CPIN and review the data from both pre-clinical animal models and from human studies with the aim of facilitating the development of appropriate strategies to prevent and/or treat CPIN.
癌症是全球第二大致死原因，也是一个主要的全球健康负担。由于辅助抗肿瘤化疗的进展，部分患者的生存率显著提高。最常用的抗肿瘤药物属于紫杉烷类、铂类和长春碱类生物碱。这些药物虽然有效，但常伴有严重的副作用，包括化疗引起的周围神经病（CPIN）。CPIN 不仅影响运动和感觉系统，而且大多数症状为感觉，主要表现为疼痛、刺痛和麻木。CPIN 不仅降低了癌症幸存者的生活质量，还可能导致治疗中断，从而对生存产生不利影响。因此，尽量减少 CPIN 的发生率或严重程度是非常理想的，但预防和/或治疗 CIPN 的策略一直难以实现。未能实现这一目标的一个困难是，导致 CPIN 的分子和细胞机制尚未完全了解；然而，一个常见的机制似乎是初级感觉神经元中离子通道表达的变化。导致化疗诱导的离子通道表达和功能变化的过程还知之甚少。并非所有抗肿瘤药物都直接影响离子通道功能，这表明其他途径可能有助于 CPIN 的发展。事实上，有迹象表明，这些药物可能通过细胞信号通路（包括第二信使和炎性细胞因子）发挥其作用。在这里，我们重点关注离子通道病作为 CPIN 的因果机制，并回顾来自临床前动物模型和人类研究的数据，旨在促进制定预防和/或治疗 CPIN 的适当策略。
