Cisplatin-Induced Ototoxicity: Updates on Molecular Targets

Trends Mol Med. 2019 Dec;25(12):1123-1132. doi: 10.1016/j.molmed.2019.08.002. Epub 2019 Aug 28.


Cis-diamminedichloridoplatinum (II) (cisplatin) is a chemotherapeutic drug currently prescribed for the treatment of many types of human cancer, but its use is associated with numerous adverse effects, one of which is ototoxicity. Cisplatin-induced hearing loss is mainly attributed to oxidative stress, but recent data suggest that inflammation could be the trigger event leading to inner ear cell death through endoplasmic reticulum (ER) stress, autophagy, necroptosis, and then intrinsic apoptosis. In this review, we look at the molecular targets of cisplatin, and the intracellular pathways underlying its ototoxicity. Special attention is devoted to signal transduction processes involving cisplatin that may promote the development of new strategies to prevent cisplatin-induced hearing loss, an adverse event with severe social impacts.

Keywords: ROS; apoptosis; autophagy; cisplatin; inflammation; ototoxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cisplatin / adverse effects*
  • Hearing Loss / chemically induced*
  • Hearing Loss / metabolism
  • Hearing Loss / pathology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Oxidative Stress / drug effects


  • Antineoplastic Agents
  • Cisplatin