Bridging the gap: mechanisms and novel translational strategies to prevent cisplatin-induced ototoxicity

Cisplatin is a widely used chemotherapeutic agent, but its clinical utility is limited by dose-dependent ototoxicity, causing irreversible sensorineural hearing loss and significantly impairing quality of life, especially in pediatric patients. This review aims to systematically examines the molecular mechanisms underlying cisplatin-induced ototoxicity and evaluate both current and emerging preventive strategies. We find that the central pathological process involves a self-perpetuating cycle of oxidative stress and immune-inflammatory responses within the cochlea, ultimately triggering the programmed death of hair cells. We critically appraise current pharmacological interventions, noting that while antioxidants, anti-inflammatory agents, and targeted delivery strategies demonstrate partial protection, their efficacy is constrained by single-target approaches, trade-offs between efficacy and safety, and interpatient variability. In contrast, emerging strategies-including nanotechnology-based drug delivery, gene therapy, epigenetic modulation, stem cell transplantation, and artificial intelligence-driven personalized interventions-offer multi-mechanistic, targeted, and potentially more effective alternatives. These emerging strategies, grounded in a detailed understanding of the core mechanisms, highlight the need for integrative, precision-focused otoprotective strategies and provide a theoretical foundation to guide future translational research.