DF2726A, a new IL-8 signalling inhibitor, is able to counteract chemotherapy-induced neuropathic pain
DF2726A, a new IL-8 signalling inhibitor, is able to counteract chemotherapy-induced neuropathic pain
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DOI：
10.1038/s41598-019-48231-z
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发表时间：
2019-08-13
影响因子：
4.6
通讯作者：
Allegretti, Marcello
中科院分区：
文献类型：
--
作者：
Brandolini, Laura;Castelli, Vanessa;Allegretti, Marcello
化疗引起的周围神经病变（CIPN）是几种抗肿瘤药物常见的剂量限制性副作用，也是癌症幸存者感觉障碍的主要原因，对患者的生活质量产生负面影响。周围神经变性或小纤维神经病通常被认为是 CIPN 发生的潜在机制。最近的证据有助于阐明细胞因子和趋化因子在导致神经元过度兴奋的过程中的决定性作用。接触奥沙利铂会引发先前与 IL-8 通路相关的周围神经病理通路的改变。我们研究了一种新型选择性 IL-8 受体抑制剂 DF2726A，并显示了其对抗 CINP 通路的作用，将 IL-8 通路激活的相关性扩展到铂类化疗药物。根据我们的结果，我们认为 DF2726A 由于其功效和优化的药代动力学/药效学特征，可能成为 CIPN 疾病临床治疗的有前途的候选药物。
Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of several anti-neoplastics and a main cause of sensory disturbances in cancer survivors, negatively impacting patients' quality of life. Peripheral nerve degeneration or small fibre neuropathy is generally accepted as the underlying mechanism in the development of CIPN. Recent evidence has contributed to clarify the determinant role of cytokines and chemokines in the process leading to neuronal hyperexcitability. Exposure to oxaliplatin triggers alterations in peripheral neuropathic pathways previously linked to IL-8 pathway. We investigated a novel selective inhibitor of IL-8 receptors, DF2726A, and showed its effects in counteracting CINP pathways, extending the relevance of the activation of IL-8 pathway to the class of platinum chemotherapeutics. Based on our results, we suggest that DF2726A might be a promising candidate for clinical treatment of CIPN conditions due to its efficacy and optimized pharmacokinetic/pharmacodynamic profile.