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
Summary
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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