Multidrug resistance

Jeffrey A. Moscow, Kenneth H Cowan

Research output: Contribution to journalReview article

394 Citations (Scopus)

Abstract

The ability of malignant cells to develop resistance to cytotoxic drugs poses a major obstacle to the ultimate success of cancer therapy. While some mechanisms of resistance allow cells to survive exposure to a single agent, the phenomenon of multidrug resistance (MDR) confers upon cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. MDR has been strongly linked to the overexpression of a membrane-associated glycoprotein, P-glycoprotein, which appears to play a role in drug efflux. However, several lines of evidence suggest that other mechanisms of resistance are involved in MDR; biochemical similarities observed in a human breast cancer cell line after the acquisition of MDR and in carcinogen-induced rat preneoplastic hepatic nodules indicate that changes in regulation of phase I and phase II drug-metabolizing enzymes may also play a role in MDR. An atypical pattern of MDR has been characterized and related to altered topoisomerase activity. Improvement in current cancer chemotherapy may be achieved by interfering with the regulation and expression of mechanisms of MDR. [J Natl Cancer Inst 1988;80:14-20].

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalJournal of the National Cancer Institute
Volume80
Issue number1
DOIs
StatePublished - Mar 2 1988

Fingerprint

Multiple Drug Resistance
Pharmaceutical Preparations
Neoplasms
Membrane Glycoproteins
P-Glycoprotein
Carcinogens
Antineoplastic Agents
Breast Neoplasms
Drug Therapy
Cell Line
Liver
Enzymes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Multidrug resistance. / Moscow, Jeffrey A.; Cowan, Kenneth H.

In: Journal of the National Cancer Institute, Vol. 80, No. 1, 02.03.1988, p. 14-20.

Research output: Contribution to journalReview article

Moscow, Jeffrey A. ; Cowan, Kenneth H. / Multidrug resistance. In: Journal of the National Cancer Institute. 1988 ; Vol. 80, No. 1. pp. 14-20.
@article{06f9c8c434c34f8b8aa414b70d302c5a,
title = "Multidrug resistance",
abstract = "The ability of malignant cells to develop resistance to cytotoxic drugs poses a major obstacle to the ultimate success of cancer therapy. While some mechanisms of resistance allow cells to survive exposure to a single agent, the phenomenon of multidrug resistance (MDR) confers upon cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. MDR has been strongly linked to the overexpression of a membrane-associated glycoprotein, P-glycoprotein, which appears to play a role in drug efflux. However, several lines of evidence suggest that other mechanisms of resistance are involved in MDR; biochemical similarities observed in a human breast cancer cell line after the acquisition of MDR and in carcinogen-induced rat preneoplastic hepatic nodules indicate that changes in regulation of phase I and phase II drug-metabolizing enzymes may also play a role in MDR. An atypical pattern of MDR has been characterized and related to altered topoisomerase activity. Improvement in current cancer chemotherapy may be achieved by interfering with the regulation and expression of mechanisms of MDR. [J Natl Cancer Inst 1988;80:14-20].",
author = "Moscow, {Jeffrey A.} and Cowan, {Kenneth H}",
year = "1988",
month = "3",
day = "2",
doi = "10.1093/jnci/80.1.14",
language = "English (US)",
volume = "80",
pages = "14--20",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Multidrug resistance

AU - Moscow, Jeffrey A.

AU - Cowan, Kenneth H

PY - 1988/3/2

Y1 - 1988/3/2

N2 - The ability of malignant cells to develop resistance to cytotoxic drugs poses a major obstacle to the ultimate success of cancer therapy. While some mechanisms of resistance allow cells to survive exposure to a single agent, the phenomenon of multidrug resistance (MDR) confers upon cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. MDR has been strongly linked to the overexpression of a membrane-associated glycoprotein, P-glycoprotein, which appears to play a role in drug efflux. However, several lines of evidence suggest that other mechanisms of resistance are involved in MDR; biochemical similarities observed in a human breast cancer cell line after the acquisition of MDR and in carcinogen-induced rat preneoplastic hepatic nodules indicate that changes in regulation of phase I and phase II drug-metabolizing enzymes may also play a role in MDR. An atypical pattern of MDR has been characterized and related to altered topoisomerase activity. Improvement in current cancer chemotherapy may be achieved by interfering with the regulation and expression of mechanisms of MDR. [J Natl Cancer Inst 1988;80:14-20].

AB - The ability of malignant cells to develop resistance to cytotoxic drugs poses a major obstacle to the ultimate success of cancer therapy. While some mechanisms of resistance allow cells to survive exposure to a single agent, the phenomenon of multidrug resistance (MDR) confers upon cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. MDR has been strongly linked to the overexpression of a membrane-associated glycoprotein, P-glycoprotein, which appears to play a role in drug efflux. However, several lines of evidence suggest that other mechanisms of resistance are involved in MDR; biochemical similarities observed in a human breast cancer cell line after the acquisition of MDR and in carcinogen-induced rat preneoplastic hepatic nodules indicate that changes in regulation of phase I and phase II drug-metabolizing enzymes may also play a role in MDR. An atypical pattern of MDR has been characterized and related to altered topoisomerase activity. Improvement in current cancer chemotherapy may be achieved by interfering with the regulation and expression of mechanisms of MDR. [J Natl Cancer Inst 1988;80:14-20].

UR - http://www.scopus.com/inward/record.url?scp=0023837668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023837668&partnerID=8YFLogxK

U2 - 10.1093/jnci/80.1.14

DO - 10.1093/jnci/80.1.14

M3 - Review article

VL - 80

SP - 14

EP - 20

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 1

ER -