title: Cisplatin-induced ototoxicity: transporters playing a role in cisplatin toxicity.
abstract: Cisplatin is a potent antineoplastic agent widely used for a variety of cancer types. Unfortunately, its use leads to dose limiting side effects such as ototoxicity. Up to 93% of patients receiving cisplatin chemotherapy will develop progressive and irreversible sensorineural hearing loss which leads to a decreased quality of life in cancer survivors. No treatment is currently available for cisplatin-induced ototoxicity. It appears that cisplatin causes apoptosis by binding DNA, activating the inflammatory cascade as well as generating oxidative stress in the cell. Various studies have aimed to assess the potential protective effects of compounds such as antioxidants, anti-inflammatories, caspase inhibitors, anti-apoptotic agents and calcium channel blockers against the toxicity caused by cisplatin in the inner ear with variable degrees of protection. Nevertheless, the pathophysiology of cisplatin-induced ototoxicity remains unclear. This review summarizes all of the known transporters that could play a role in cisplatin influx, leading to cisplatin-induced ototoxicity. The following were evaluated: copper transporters, organic cation transporters, the transient receptor potential channel family, calcium channels, multidrug resistance associated proteins, mechanotransduction channels and chloride channels.
authors: Department of Otolaryngology, The Montreal Children's Hospital, Quebec, Canada.
authors: Sofia
authors: S
authors: Waissbluth
authors: Sam J
authors: SJ
authors: Daniel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002945:Cisplatin / Q000009:adverse effects* / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D020011:Protective Agents; D002945:Cisplatin