Keynote address: Multidrug resistance: A pleiotropic response to cytotoxic drugs

Craig R. Fairchild, Kenneth H. Cowan

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Tumor cells exposed in tissue culture to one of several different classes of antineoplastic agents, including anthracyclines, vinca alkaloids, epipodophyllotoxins, and certain antitumor antibiotics, can develop resistance to the selecting agent and cross resistance to the other classes of agents. This phenomena of multidrug resistance is generally associated with decreased drug accumulation and overexpression of a membrane glycoprotein. This membrane protein, referred to as P-glycoprotein, apparently acts as an energy-dependent drug efflux pump. Multidrug resistance in human MCF-7 breast cancer cells selected for resistance to adriamycin (AdrR MCF-7) is associated with amplification and overexpression of the mdrl gene which encodes P-glycoprotein. A number of other changes are also seen in this resistant cell line including alterations in Phase I and Phase II drug metabolizing enzymes. Similar biochemical changes occur in a rat model for hepatocellular carcinogenesis and are associated in that system with broad spectrum resistance to hepatotoxins. The similar changes in these two models of resistance suggests that these changes might be part of a battery of genes whose expression can be altered in response to cytotoxic stress, thus rendering the cell resistant to a wide variety of cytotoxic agents.

Original languageEnglish (US)
Pages (from-to)361-367
Number of pages7
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume20
Issue number2
DOIs
StatePublished - Feb 1991
Externally publishedYes

Keywords

  • Glutathione S-transferase
  • Hyperoplastic liver nodules
  • Multidrug resistance
  • P-glycoprotein
  • Xenobiotic resistance

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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