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The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance
1Children's Cancer Research Institute, Sydney Children's Hospital, Randwick, NSW, Australia.
Abstract:
Multidrug resistance (MDR) is a major hindrance to the successful treatment of neoplastic disease. The development of resistance to multiple chemotherapeutic drugs is a complex phenomenon which has been described in both tumor cell lines and human cancers. To date, two mechanisms associated with overexpression of membrane glycoproteins that function as energy-dependent efflux pumps to reduce intracellular drug levels have been identified for MDR. The first described was the product of the MDR1 gene, P-glycoprotein. The second mechanism is mediated by overexpression of the multidrug resistance-associated protein (MRP). While these proteins both belong to the ATP-binding cassette superfamily of transporters, they are only distantly related. Despite this low homology, they mediate resistance to a similar range of chemotherapeutic drugs. While P-glycoprotein has been well described in the literature, much less is known about the recently identified MRP. This review gives an overview of the characteristics of MRP at both the phenotypic and genotypic levels, and discusses its possible relevance in drug-refractory cancer.
Insights
Multidrug resistance (MDR) poses a significant challenge in cancer treatment. This review details the multidrug resistance-associated protein (MRP), a key factor in chemotherapy resistance, and its role in drug-refractory cancers.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Multidrug resistance (MDR) is a major obstacle in treating neoplastic diseases.
- MDR involves resistance to multiple chemotherapeutic drugs, observed in cell lines and human cancers.
- Two primary mechanisms for MDR involve efflux pumps: P-glycoprotein (MDR1 gene product) and multidrug resistance-associated protein (MRP).
Purpose of the Study:
- To provide an overview of the multidrug resistance-associated protein (MRP).
- To describe the phenotypic and genotypic characteristics of MRP.
- To discuss the potential relevance of MRP in drug-refractory cancers.
Main Methods:
- Literature review of existing studies on multidrug resistance mechanisms.
- Analysis of phenotypic characteristics associated with MRP.
- Examination of genotypic data related to MRP expression.
Main Results:
- MRP, like P-glycoprotein, belongs to the ATP-binding cassette superfamily of transporters.
- Despite low homology with P-glycoprotein, MRP mediates resistance to a similar range of chemotherapeutic drugs.
- Less is known about MRP compared to P-glycoprotein, highlighting a gap in current understanding.
Conclusions:
- MRP is a significant factor in multidrug resistance in cancer.
- Understanding MRP's characteristics is crucial for addressing drug-refractory cancers.
- Further research into MRP may reveal new therapeutic strategies for overcoming chemotherapy resistance.