The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy

Annu Rev Pharmacol Toxicol. 2008;48:495-535. doi: 10.1146/annurev.pharmtox.48.080907.180426.

Abstract

The platinum (Pt) drugs cisplatin and carboplatin are heavily employed in chemotherapy regimens; however, similar to other classes of drugs, a number of intrinsic and acquired resistance mechanisms hamper their effectiveness. The method by which Pt drugs enter cells has traditionally been attributed to simple passive diffusion. However, recent evidence suggests a number of active uptake and efflux mechanisms are at play, and altered regulation of these transporters is responsible for the reduced accumulation of drug in resistant cells. This review suggests a model that helps reconcile the disparate literature by describing multiple pathways for Pt-containing drugs into and out of the cell.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Carboplatin / pharmacokinetics
  • Carboplatin / pharmacology
  • Cell Membrane / metabolism
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Membrane Transport Proteins / metabolism
  • Platinum Compounds / pharmacokinetics*
  • Platinum Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Membrane Transport Proteins
  • Platinum Compounds
  • Carboplatin
  • Cisplatin