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[Multidrug resistance (MDR) in oncology]
A Souvirón Rodríguez1, M J Ruiz Gómez, J A Morales Moreno
1Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga.
Anales De Medicina Interna (Madrid, Spain : 1984)
|March 1, 1997
Summary
Multidrug resistance (MDR) in cancer is often caused by the MDR1 gene, which produces p-glycoprotein (Pgp) pumps that expel chemotherapy drugs. Researchers are developing drugs to inhibit these pumps and overcome treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy, leading to treatment failure.
- MDR is frequently associated with the overexpression of the MDR1 gene, encoding p-glycoprotein (Pgp).
- Pgp acts as an ATP-dependent efflux pump, reducing intracellular drug concentrations and rendering cancer cells resistant.
Purpose of the Study:
- To review the mechanisms of MDR, focusing on Pgp.
- To explore diagnostic strategies for detecting MDR.
- To discuss therapeutic approaches for reversing MDR.
Main Methods:
- Review of literature on MDR mechanisms, diagnostics, and therapeutics.
- Identification of key genes (MDR1) and proteins (Pgp) involved in MDR.
- Analysis of current and potential MDR reversal agents and strategies.
Main Results:
- MDR1 gene and Pgp are central to MDR, acting as drug efflux pumps.
- Various diagnostic methods exist, including gene detection, mRNA analysis, and Pgp detection via flow cytometry, Western blot, and immunohistochemistry.
- Several agents, like verapamil and cyclosporine derivatives, inhibit Pgp, with ongoing clinical trials showing mixed results.
Conclusions:
- MDR remains a major obstacle in cancer treatment, primarily due to Pgp-mediated drug efflux.
- Effective diagnostic tools are available for identifying MDR.
- Further development of potent, well-tolerated MDR modulators, alongside novel therapeutic strategies like gene therapy and targeted drug delivery, is crucial for improving patient outcomes.