Platinum accumulation in chemotherapy: toxicity mechanisms, challenges, and mitigation strategies

Platinum-based chemotherapeutic agents constitute the cornerstone of treatment for a wide range of solid tumors. However, residual platinum can persist in the body long after treatment cessation, leading to progressive accumulation, chronic multi-system toxicity, and significant impairment of patients' quality of life. The insidious onset and lack of specific monitoring methods often lead to the oversight of this treatment-related metal accumulation toxicity. This article reviews the environmental and occupational exposure risks of platinum, its unique pharmacokinetic properties, and elucidates how its irreversible binding to proteins and accumulation within mitochondria form the chemical basis for its long-term toxicity. It further elaborates on the core mechanisms underlying platinum accumulation-mediated multi-organ toxicity, including nephrotoxicity, neurotoxicity, and ototoxicity. The aim is to provide insights and directions for improving the long-term prognosis of cancer survivors by clarifying the toxicological mechanisms, clinical impacts, and future strategies for mitigating platinum-induced metal accumulation.