The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy.
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.
Hall
Matthew D
MD
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Okabe
Mitsunori
M
Shen
Ding-Wu
DW
Liang
Xing-Jie
XJ
Gottesman
Michael M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D016190:Carboplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D017671:Platinum Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology
D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D017671:Platinum Compounds; D016190:Carboplatin; D002945:Cisplatin