Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis

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.