The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy.
The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy.
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DOI：
10.3389/fnmol.2017.00397
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发表时间：
2017
影响因子：
4.8
通讯作者：
Malcangio M
中科院分区：
文献类型：
--
作者：
Montague K;Malcangio M
在癌症治疗中，化疗药物的剂量限制性副作用是产生神经性疼痛，目前临床上可用的药物对此治疗效果不佳。化疗引起的疼痛性神经病（CIPN）是过早停止治疗的主要原因，因此非常需要更好地了解其潜在机制并开发新的、更有效的疗法。在某些情况下，临床和临床前仅观察到化疗引起的疼痛与神经元损伤之间存在微弱的相关性。因此，非神经元细胞（例如免疫细胞）及其与 CIPN 中神经元的通信的关键作用最近受到重视。在这篇小综述中，我们将讨论 CIPN 中外周单核细胞/巨噬细胞作用的临床前证据，重点关注与化疗药物长春新碱和紫杉醇相关的证据。此外，我们将讨论在这种情况下调节单核细胞/巨噬细胞-神经元串扰的潜在机制。根据临床前数据，我们还将考虑单核细胞/巨噬细胞作为CIPN临床治疗靶点的价值。本综述中讨论的操纵信号通路的方法既显示出希望，也显示出潜在的陷阱。尽管如此，它们正在成为创新的治疗靶点，CX3CL1/R1 对单核细胞/巨噬细胞-神经元通讯的调节目前正成为有前途的领跑者。
In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN) is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically. As such, a critical role for non-neuronal cells, such as immune cells, and their communication with neurons in CIPN has recently been appreciated. In this mini-review, we will discuss preclinical evidence for the role of monocytes/macrophages in the periphery in CIPN, with a focus on that which is associated with the chemotherapeutic agents vincristine and paclitaxel. In addition we will discuss the potential mechanisms that regulate monocyte/macrophage–neuron crosstalk in this context. Informed by preclinical data, we will also consider the value of monocytes/macrophages as therapeutic targets for the treatment of CIPN clinically. Approaches that manipulate the signaling pathways discussed in this review show both promise and potential pitfalls. Nonetheless, they are emerging as innovative therapeutic targets with CX3CL1/R1-regulation of monocyte/macrophage–neuron communication currently emerging as a promising front-runner.
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影响因子：
8.1
作者：
Imai T;Yasuda N
通讯作者：
Yasuda N
影响因子：
3.8
作者：
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Woodroofe, M. Nicola
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7.6
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通讯作者：
Hargreaves, K. M.