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Mechanisms of cancer drug resistance

Michael M Gottesman1

  • 1Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892-4255, USA. mgottesman@nih.gov

Annual Review of Medicine
|January 31, 2002
PubMed

Insights

Cancer drug resistance is a major challenge, often caused by drug transporters ejecting chemotherapy from cells. Understanding these mechanisms is key to improving cancer treatment effectiveness.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Despite advances in cancer chemotherapy, no treatment is universally effective against disseminated cancer.
  • Cancer drug resistance, both intrinsic and acquired, presents a significant obstacle in treatment.
  • Factors contributing to resistance include patient variability and tumor genetic differences.

Purpose of the Study:

  • To review the mechanisms underlying anticancer drug resistance.
  • To explore strategies for overcoming cancer drug resistance.
  • To discuss the implications of resistance mechanisms for drug pharmacokinetics.

Main Methods:

  • Literature review of studies on cancer drug resistance mechanisms.
  • Analysis of factors contributing to intrinsic and acquired resistance.
  • Examination of the role of transporters, apoptosis, and drug metabolism in resistance.

Main Results:

  • Energy-dependent transporters are a primary cause of acquired resistance by ejecting drugs from cancer cells.
  • Insensitivity to drug-induced apoptosis and drug-detoxifying mechanisms also contribute significantly to resistance.
  • Understanding these resistance pathways provides insights into improving chemotherapy efficacy.

Conclusions:

  • Elucidating cancer drug resistance mechanisms is crucial for developing more effective cancer therapies.
  • Targeting resistance pathways, such as transporter activity, offers potential therapeutic strategies.
  • Knowledge of resistance mechanisms impacts the pharmacokinetic profiles of anticancer drugs.

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