Journal
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
Volume 40, Issue 2, Pages 426-435Publisher
FIELD HOUSE PUBLISHING LLP
DOI: 10.1177/147323001204000204
Keywords
MULTIPLE DRUG RESISTANCE (MDR); SIGNAL TRANSDUCTION PATHWAY; P-GLYCOPROTEIN; ABCB1; CANCER
Funding
- Science and Technology Commission of Shanghai Municipality [10ZR1427400, 07ZR14111, 10140902600]
- Shanghai Municipal Education Commission [09YZ132]
- Shanghai Third Leading Academic Discipline Project [S30302]
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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 NH2-terminal kinase (JNK), p38, cyclic adenosine monophosphate-dependent protein kinase, phosphatidylinositol 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.
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