DF2726A, a new IL-8 signalling inhibitor, is able to counteract chemotherapy-induced neuropathic pain

DF2726A 是一种新型 IL-8 信号抑制剂,能够抵消化疗引起的神经性疼痛

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作者:Laura Brandolini, Vanessa Castelli, Andrea Aramini, Cristina Giorgio, Gianluca Bianchini, Roberto Russo, Carmen De Caro, Michele d'Angelo, Mariano Catanesi, Elisabetta Benedetti, Antonio Giordano, Annamaria Cimini, Marcello Allegretti

Abstract

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.

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