Chemotherapy-induced peripheral neuropathy: Pathophysiology, clinical impact and future perspectives in oncology care

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity associated with several neurotoxic chemotherapeutic agents. While targeting malignant cells, these chemotherapeutic agents also initiate several neurotoxic mechanisms such as structural damage to axons, mitochondrial dysfunction, oxidative injury, and inflammatory responses within the peripheral nervous system. This narrative review dissects the mechanistic underpinnings of CIPN, quantifies its substantial clinical burden on cancer survivors, evaluates evidence-based prevention strategies, and provides a future perspective in oncology care. A comprehensive literature synthesis was performed across “Google Scholar”, “PubMed” and “Scopus” with the following keywords such as “CIPN mechanisms,” “Peripheral Neuropathy,” and “CIPN,” preclinical, clinical and epidemiological investigations addressing CIPN pathogenesis, clinical manifestations, risk factors and mitigation approaches were included, excluding non-English publications and studies lacking direct relevance to neurotoxic chemotherapy outcomes. The results were categorised into mechanistic, clinical, and preventative areas using a thematic analysis. Through microtubule disruption, mitochondrial dysfunction, ion channel dysregulation, and persistent neuroinflammation, mechanistic investigations demonstrate the complex pathophysiology of CIPN, which primarily affects length-dependent sensory neurones. Clinically, CIPN causes gait instability, chronic neuropathic pain, and lasting distal sensory impairments in 30–70% of exposed patients. It also lowers treatment outcomes, frequently necessitating dose reductions that jeopardise oncologic efficacy. Risk stratification is made possible by new pharmacogenomic and AI-driven prediction models, structured exercise preserves neuromuscular function, cryotherapy decreases taxane-associated risk by up to half for the individual, and preventive therapies show varying success. These results highlight the advantages of targeted prevention versus symptomatic treatment alone.