title: Cisplatin : an old drug with a newfound efficacy -- from mechanisms of action to cytotoxicity.
abstract: BACKGROUND
  Cisplatin is a highly effective antineoplastic drug with an extremely current mechanism of action. Cisplatin-induced side effects are dose-dependent and limit the administration of increased dosages, thus compromising its therapeutic efficacy.
  
  
  METHODS
  This review aims to describe the emerging knowledge about the biochemical mechanisms that mediate cisplatin cytotoxicity and side effects. A specific section is devoted to discuss the pathogenesis of cisplatin-related toxicities and the potential measures to counteract them.
  
  
  CONCLUSIONS
  Although cisplatin has been used for a long time, only recently its exact mechanism of action has been better defined. The cytotoxic activity of cisplatin is largely dependent on the glycolytic metabolism of tumor cells: cisplatin redirects cancer cells to oxidative phosphorylation from the 'Warburg effect', which is considered one of the most important mechanisms of tumor cell survival. The interference of cisplatin with glucose metabolism is also a cause of its relevant toxicities. The emerging knowledge on the complex mechanisms, which mediate cisplatin cytotoxicity and side effect, may lead to a more appropriate and safe use of this drug. Further studies are warranted to define and implement its effectiveness in combination with targeted drugs able to interfere with cellular energy metabolism, such as mTOR inhibitors.
authors.affiliation: Businco Hospital, Department of Gynecologic Oncology, Businco Hospital, Regional Referral Center for Cancer Disease Cagliari, Italy. a.maccio@tin.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Macciò
authors.forename: Clelia
authors.initials: C
authors.lastname: Madeddu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin