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Multidrug resistance during cancer chemotherapy--biotechnological solutions to a clinical problem
1Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, UK.
Abstract:
Tumour cells can be resistant to a variety of chemotherapeutic drugs of different structure (multidrug resistance) by expressing a transmembrane pump (P-glycoprotein) on their cell surface. This situation can lead to a failure of cancer chemotherapy as the P-glycoprotein acts by actively pumping the drugs out of cells, thus lowering the intracellular concentration of the drug and, hence, its cytotoxic effectiveness. This review summarizes present and proposed approaches to preventing or circumventing the action of this drug-transporting protein.
Insights
Multidrug resistance in cancer occurs when tumour cells express P-glycoprotein, a pump that removes chemotherapy drugs. This review explores strategies to overcome this common challenge in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy.
- Tumour cells express P-glycoprotein (P-gp), a transmembrane efflux pump, conferring resistance to various chemotherapeutic agents.
- P-gp actively transports drugs out of cancer cells, reducing intracellular drug concentration and therapeutic efficacy.
Purpose of the Study:
- To review current and proposed strategies for overcoming P-glycoprotein-mediated multidrug resistance.
- To summarize approaches that prevent or circumvent the action of the P-gp efflux pump.
- To provide an overview of potential therapeutic interventions against MDR in cancer.
Main Methods:
- Literature review of existing research on P-glycoprotein and multidrug resistance.
- Analysis of current clinical and preclinical strategies targeting P-gp.
- Synthesis of proposed novel approaches to circumvent P-gp function.
Main Results:
- P-glycoprotein expression is a key mechanism of multidrug resistance in various cancers.
- Several strategies exist to inhibit P-gp activity or expression.
- Emerging approaches aim to bypass P-gp efflux or target resistant cells specifically.
Conclusions:
- Overcoming P-glycoprotein-mediated multidrug resistance is crucial for improving cancer treatment outcomes.
- Combination therapies involving P-gp inhibitors or modulators show promise.
- Further research into novel circumvention strategies is warranted to enhance chemotherapy effectiveness.