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Targeting multidrug resistance in cancer

Gergely Szakács1, Jill K Paterson, Joseph A Ludwig

  • 1Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest Karolina út 29; H-1518 Hungary.

Nature Reviews. Drug Discovery
|March 7, 2006
PubMed

Insights

Multidrug resistance in metastatic cancers is a major challenge, often caused by ATP-binding cassette (ABC) transporters that pump drugs out of cancer cells. Strategies to overcome this involve targeting these transporters to improve chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metastatic cancer treatment frequently relies on chemotherapy, but its efficacy is limited by drug resistance.
  • Simultaneous resistance to multiple chemotherapy agents, known as multidrug resistance (MDR), necessitates the use of combination therapies.
  • Understanding MDR mechanisms is crucial for developing more effective cancer treatments.

Purpose of the Study:

  • To review the primary mechanisms of multidrug resistance in cancer.
  • To focus on the role of ATP-binding cassette (ABC) transporters in mediating drug efflux.
  • To discuss strategies for overcoming ABC transporter-mediated MDR.

Main Methods:

  • Literature review of established research on multidrug resistance.
  • Analysis of the function and significance of ATP-binding cassette (ABC) transporters in cancer cells.
  • Synthesis of current approaches to combatting MDR.

Main Results:

  • Drug efflux mediated by ATP-binding cassette (ABC) transporters is a predominant mechanism of multidrug resistance.
  • These transporters expel a wide range of structurally and functionally diverse chemotherapy drugs from cancer cells.
  • Various strategies are being developed to inhibit, bypass, or utilize ABC transporter activity.

Conclusions:

  • ATP-binding cassette (ABC) transporter-mediated drug efflux is a critical challenge in metastatic cancer chemotherapy.
  • Targeting ABC transporters offers promising avenues for overcoming multidrug resistance.
  • Future therapeutic strategies should aim to modulate ABC transporter function to enhance treatment outcomes.

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