Chemotherapy-induced peripheral neuropathy (CIPN): Disease mechanisms, experimental models and emerging prevention strategies

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of several classes of anticancer agents, with complex pathophysiology that is distinct from other neuropathies, such as diabetic neuropathy. Here, we provide a comprehensive review of CIPN, linking clinical presentations and implicated anticancer therapeutics to their underlying molecular mechanisms. We discuss both conventional chemotherapy agents and emerging modalities, including antibody-drug conjugates. We also critically evaluate experimental models of CIPN, spanning in vivo, ex vivo, and both classical and emerging advanced in vitro human-derived models, alongside methodological advances capable of providing deeper mechanistic insight into CIPN. Importantly, we examine current and emerging strategies for CIPN prevention, emphasising the need to prioritise prevention over symptomatic management. By integrating clinical insights, established and emerging mechanistic understanding, and a comprehensive overview of experimental models and methodological advances alongside emerging preventive interventions, this review uniquely serves as both a clinical and biological guide to CIPN. It aims to bridge the gap between bench and bedside, supporting both researchers and clinicians in advancing effective prevention strategies to combat CIPN, a significant unmet need affecting patients during treatment and throughout cancer survivorship.