Abstract
Multiple drug resistance (MDR), defined as the ability of tumour cells to survive exposure to many chemotherapeutic agents, is a major cause of treatment failure in human cancers. The membrane transporter P-glycoprotein (Pgp, encoded by the ABCB1 [adenosine triphosphate-binding cassette, subfamily B, member 1] gene) is the main mechanism for decreased intracellular drug accumulation in human MDR cancer. ABCB1/Pgp-mediated MDR involves several signal transduction pathways and transcription factors. Activation of these signal transduction pathways influences the prognosis of MDR human cancer. Signalling pathways involved in ABCB1/Pgp-mediated MDR include the mitogen-activated protein kinase (MAPK), c-Jun NH(2)-terminal kinase (JNK), p38, cyclic adenosine monophosphate-dependent protein kinase, phosphatidylino sitol 3-kinase and protein kinase C signalling pathways. This review summarizes the biological characteristics, target points and signalling cascade mediators of these pathways. Drugs targeted against these pathways may provide new therapies for treatment of ABCB1/Pgp-mediated MDR.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / therapeutic use
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Biological Transport / genetics
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Drug Resistance, Multiple / genetics
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Drug Resistance, Multiple / physiology*
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Drug Resistance, Neoplasm* / genetics
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Gene Expression Regulation, Neoplastic
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Signaling System / genetics
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MAP Kinase Signaling System / physiology*
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Neoplasms / drug therapy
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Neoplasms / genetics
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Neoplasms / metabolism*
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Phosphatidylinositol 3-Kinase / metabolism
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Protein Kinase C / metabolism
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Transcription, Genetic*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Phosphatidylinositol 3-Kinase
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Protein Kinase C
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases