Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies

Cisplatin is a highly effective antitumor drug generally used in the treatment of solid malignant tumors. However, cisplatin causes severe side effects such as bone marrow depression, nephrotoxicity, and ototoxicity, thus limiting its clinical application. The incidence of ototoxicity induced by cisplatin ranges from 20% to 70%, and it usually manifests as a progressive, bilateral and irreversible hearing loss. Although the etiology of cisplatininduced ototoxicity remains unclear, an increasing body of evidence suggests that the ototoxicity of cisplatin is mainly related to the production of reactive oxygen species and activation of apoptotic pathway in cochlear tissues. Many drugs have been well proved to protect cisplatin-induced hearing loss in vitro and in vivo. However, the anti-tumor effect of cisplatin is also weakened by systemic administration of those drugs for hearing protection, especially antioxidants. Therefore, establishing a local administration strategy contributes to the otoprotection without affecting the effect of cisplatin. This review introduces the pathology of ototoxicity caused by cisplatin, and focuses on recent developments in the mechanisms and protective strategies of cisplatin-induced ototoxicity.

Automated summary

Cisplatin, an effective antitumor drug for solid malignant tumors, is known to cause ototoxicity, which manifests as progressive, bilateral, and irreversible hearing loss. The ototoxicity is primarily related to reactive oxygen species production and activation of the apoptotic pathway in cochlear tissues. Despite protective strategies being developed, systemic administration of drugs for hearing protection may weaken cisplatin's anticancer effect.