Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurologic complication of chemotherapy, resulting in symptoms like pain, sensory loss, and numbness in the hands and feet that cause lots of uneasiness in patients with cancer. They often suffer from pain so severe that it interrupts the treatment, thus invalidating the entire chemotherapy-based healing process, and significantly reducing their quality of life. In this paper, we underline the role of the complement system in CIPN, highlighting the relevance of the C5a fragment and its receptor C5aR1, whose activation is thought to be involved in triggering a cascade of events that can lead to CIPN onset. Recent experimental data showed the ability of docetaxel and paclitaxel to specifically bind and activate C5aR1, thus shining light on one of the molecular mechanisms by which taxanes may activate a cascade of events leading to neuropathy. According to these new evidence, it was possible to suggest new mechanisms underlying the pathophysiology of CIPN. Hence, the C5a/C5aR1 axis may represent a new target for CIPN treatment, and the use of C5aR1 inhibitors can be proposed as a potential new therapeutic option to manage this high unmet medical need.

化疗引起的周围神经病变 (CIPN) 是化疗最常见的神经系统并发症，会导致疼痛、感觉丧失和手脚麻木等症状，给癌症患者带来很多不安。他们经常遭受如此严重的疼痛，以至于中断治疗，从而使整个基于化学疗法的治愈过程无效，并显着降低他们的生活质量。在本文中，我们强调了补体系统在 CIPN 中的作用，强调了 C5a 片段及其受体 C5aR1 的相关性，其激活被认为参与触发可导致 CI​​PN 发作的一系列事件。最近的实验数据表明，多西紫杉醇和紫杉醇具有特异性结合和激活 C5aR1 的能力，从而阐明了紫杉烷类可能激活导致神经病的一系列事件的分子机制之一。根据这些新证据，有可能提出 CIPN 病理生理学的新机制。因此，C5a/C5aR1 轴可能代表 CIPN 治疗的新靶点，并且可以提议使用 C5aR1 抑制剂作为潜在的新治疗选择来管理这一未满足的高度医疗需求。