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Multidrug resistance in brain tumors: roles of the blood-brain barrier
A Régina1, M Demeule, A Laplante
1Laboratoire de Médecine Moléculaire, Hôpital Sainte-Justine-Université du Québec à Montréal, Canada.
Abstract:
Malignant brain tumors and brain metastases present a formidable clinical challenge against which no significant advances have been made over the last decade. Multidrug resistance (MDR) is one of the main factors in the failure of chemotherapy against central nervous system tumors. The MDR1 gene encoding P-glycoprotein (P-gp), a drug efflux pump which plays a significant role in modulating MDR in a wide variety of human cancers, is highly expressed in the blood-brain barrier (BBB). The BBB controls central nervous system exposure to many endogenous and exogenous substances. The exact molecular mechanisms by which the BBB is involved in the resistance of brain tumors to chemotherapy remain to be identified. The purpose of this review is to summarize reports demonstrating that P-gp, one of the most phenotypically important markers of the BBB, is present in primary brain tumors and thus plays a crucial role in their clinical resistance to chemotherapy.
Insights
Multidrug resistance (MDR) in brain tumors is a major challenge. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) contributes to chemotherapy failure by pumping drugs out of the central nervous system.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Pharmacology
Background:
- Malignant brain tumors and metastases are difficult to treat, with limited therapeutic advances.
- Multidrug resistance (MDR) is a primary cause of chemotherapy failure in central nervous system (CNS) cancers.
- The MDR1 gene, encoding P-glycoprotein (P-gp), is crucial for MDR and highly expressed at the blood-brain barrier (BBB).
Purpose of the Study:
- To review evidence linking P-gp expression in primary brain tumors to chemotherapy resistance.
- To elucidate the role of the BBB and P-gp in CNS tumor treatment failure.
Main Methods:
- Literature review of studies on P-gp expression in brain tumors.
- Analysis of P-gp's function as a drug efflux pump at the BBB.
- Examination of the clinical implications of P-gp in brain tumor chemotherapy.
Main Results:
- P-glycoprotein (P-gp) is a key determinant of MDR in various cancers.
- High P-gp expression is observed in the blood-brain barrier (BBB).
- Evidence suggests P-gp is present in primary brain tumors, contributing to treatment resistance.
Conclusions:
- P-glycoprotein (P-gp) is a critical factor in the clinical resistance of brain tumors to chemotherapy.
- Understanding P-gp's role at the BBB is vital for developing effective CNS cancer treatments.
- Targeting P-gp may overcome MDR and improve chemotherapy outcomes for brain tumor patients.