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[Multiple drug resistance: a problem in cancer chemotherapy]
M Lizano Soberón1, R Barrera Rodríquez
1Depto. Inv. Básica, Instituto National de Cancerología, México D.F.
Summary
Acquired cellular drug resistance, particularly multidrug resistance (MDR) in tumors, is a major clinical oncology challenge. Increased P-glycoprotein (P-gp) expression is a key mechanism, reducing drug accumulation and leading to treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Acquired cellular drug resistance is a significant challenge in clinical oncology.
- Multidrug resistance (MDR) in tumors involves resistance to unrelated drugs, often linked to increased MDR1 gene expression.
- The plasma membrane glycoprotein P-glycoprotein (P-gp) acts as an energy-dependent efflux pump, reducing intracellular drug accumulation.
Purpose of the Study:
- To investigate the mechanisms of acquired cellular drug resistance in tumors.
- To explore the role of P-glycoprotein (P-gp) in multidrug resistance (MDR).
- To identify other contributing factors to drug resistance, such as topoisomerase II and glutathione transferase.
Main Methods:
- Biochemical and molecular methods were employed to study drug resistance mechanisms.
- Analysis of MDR1 gene expression and P-gp levels in resistant cell lines.
- Investigation of topoisomerase II and glutathione transferase alterations.
Main Results:
- Increased P-gp expression in cell lines correlated with decreased drug accumulation and retention.
- Other MDR mechanisms, including altered topoisomerase II and glutathione transferase, were identified.
- Studies suggest multiple interacting factors contribute to cellular drug resistance in human tumors.
Conclusions:
- P-glycoprotein (P-gp) is a significant factor in tumor multidrug resistance (MDR).
- Multiple, interacting mechanisms contribute to acquired cellular drug resistance.
- Understanding these mechanisms is crucial for developing strategies to overcome MDR in clinical oncology.