Multidrug resistance in cancer (review)
The development of resistance to anticancer agents during treatment is a major obstacle in the chemotherapy of cancer. Cells expressing high levels of the P-glycoprotein exhibit a multidrug resistance phenotype. The P-glycoprotein is a membrane phosphoprotein which serves as a drug efflux pump to reduce intracellular drug accumulation, and hence the cytotoxicity of anticancer drugs. Several studies have shown that protein kinase activators and inhibitors may modulate the biological activity of P-glycoprotein through covalent modification by phosphorylation. Most of these drugs may have additional mechanisms of action and may alter drug accumulation within multidrug resistant cells with or without their effects on phosphorylation of P-glycoprotein. In addition, transcriptional regulation of MDR 1 gene has been found to be regulated by protein kinase A type I and protein kinase C. Therefore, these kinases may be important candidates in studies of the reversal of multidrug resistance and hence in enhancing the efficacy of anticancer drugs.
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Document Type: Research Article
Affiliations: NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892.
Publication date: November 1, 1996
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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