Dompé Farmaceutici SpA, Via Campo di Pile, L'Aquila, Italy.
Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Sci Rep. 2019 Aug 13;9(1):11729. doi: 10.1038/s41598-019-48231-z.
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.
化疗引起的周围神经病（CIPN）是几种抗肿瘤药物的常见剂量限制副作用，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。外周神经退行性变或小纤维神经病通常被认为是 CIPN 发展的潜在机制。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。奥沙利铂的暴露会引发先前与 IL-8 途径相关的外周神经性途径的改变。我们研究了一种新型的 IL-8 受体选择性抑制剂 DF2726A，并显示其在对抗 CINP 途径方面的作用，将 IL-8 途径的激活扩展到铂类化疗药物。基于我们的结果，我们认为由于其疗效和优化的药代动力学/药效学特征，DF2726A 可能是治疗 CIPN 疾病的有前途的候选药物。
