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Multidrug resistance: prospects for clinical management
A Mansouri1, K J Henle, W A Nagle
1Medical Research Service 151, John L. McClellan Memorial Veterans Hospital, Little Rock.
SAAS Bulletin, Biochemistry and Biotechnology
|January 1, 1992
Summary
Cancer cells develop multiple drug resistance (MDR) through various mechanisms beyond classical P-170 pumps. Targeting these diverse resistance pathways is key to overcoming treatment failures in chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Chemotherapy has improved cancer treatment, but drug resistance remains a significant challenge.
- Classical multiple drug resistance (MDR) involves P-170 glycoprotein pumps that export drugs.
- MDR is a complex phenomenon involving multiple cellular mechanisms beyond P-170.
Purpose of the Study:
- To review evidence supporting diverse mechanisms of MDR in cancer cells.
- To discuss strategies for overcoming drug resistance by targeting these mechanisms.
Main Methods:
- Literature review of recent evidence on MDR mechanisms.
- Discussion of potential therapeutic strategies targeting MDR.
Main Results:
- MDR involves various mechanisms including other efflux pumps, GSH conjugation, DNA repair, gene amplification, and oncogene activation.
- These mechanisms can be variable and independent across different cancer cell lines.
- Identifying specific resistance mechanisms is crucial for effective treatment reversal.
Conclusions:
- Reversing drug resistance requires targeting the specific operative mechanisms.
- Potential strategies include competitive inhibition of P-170, selective energy depletion, or tumor cell permeabilization to bypass efflux pumps.