An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

• Differing mechanisms of platinum-induced cytotoxicity are introduced.
• Known pathways of cisplatin-induced nephrotoxicity are discussed.
• Known mechanisms and cochlear sites of cisplatin-induced ototoxicity are reviewed.
• Examples of risk factors enhancing cisplatin-induced ototoxicity are highlighted.
• Potential strategies to reduce cisplatin-induced ototoxicity are introduced.

Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations.