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Is p-glycoprotein a potential target for reversing clinical drug resistance?
1University of Arizona, College of Medicine, Arizona Cancer Center, Tucson 85724.
Abstract:
The overexpression of MDR1 p-glycoprotein has been associated with the emergence of clinical drug resistance for a number of malignancies, especially those of the hematopoietic variety. Given this observation, the question arises regarding the suitability of p-glycoprotein as a target for reversing multiple drug resistance (MDR) and improving therapeutic outcome. This review focuses on the role of p-glycoprotein in hematopoietic malignancies and proposes that these malignancies serve as a prototype for further investigations. The status of clinical studies to reverse or circumvent clinical MDR is also discussed. Recommendations are made regarding the kinds of tumors to be studied, the type of chemosensitizer desired, and the design of clinical protocols required to answer the question of whether p-glycoprotein is a suitable target to reverse or prevent clinical MDR.
Insights
P-glycoprotein overexpression drives drug resistance in hematopoietic cancers. This review examines targeting p-glycoprotein to overcome multiple drug resistance (MDR) and improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer therapy.
- Overexpression of MDR1 p-glycoprotein is linked to treatment failure in various cancers, particularly hematologic malignancies.
- The role of p-glycoprotein in drug resistance necessitates evaluating its potential as a therapeutic target.
Purpose of the Study:
- To review the role of p-glycoprotein in hematopoietic malignancies.
- To assess the suitability of p-glycoprotein as a target for reversing MDR.
- To provide recommendations for future clinical studies investigating p-glycoprotein inhibition.
Main Methods:
- Literature review of studies on p-glycoprotein and MDR in hematopoietic malignancies.
- Analysis of current clinical trials aimed at reversing or circumventing MDR.
- Synthesis of data to evaluate the efficacy of p-glycoprotein as a therapeutic target.
Main Results:
- Hematopoietic malignancies serve as a key model for studying p-glycoprotein-mediated MDR.
- Clinical studies are exploring various strategies to overcome p-glycoprotein-driven resistance.
- The effectiveness of p-glycoprotein as a target requires further rigorous investigation.
Conclusions:
- P-glycoprotein is a critical factor in MDR, especially in hematologic cancers.
- Targeting p-glycoprotein holds promise for improving therapeutic outcomes in MDR.
- Careful selection of tumor types, chemosensitizers, and clinical trial designs are essential to validate p-glycoprotein as a viable therapeutic target.