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Abstract
The intrinsic or acquired resistance to anticancer drugs remains one of the most significant factors impeding the progress of cancer chemotherapy. This phenomenon often involves simultaneous resistance to other anticancer drugs that differ in their chemical structure and mode of action and are not even used in chemotherapy. This phenotype has been called multidrug resistance (MDR). Although the cellular basis underlying MDR is not fully understood, several factors mediating therapy resistance in tumors have been proposed. One of the mechanisms leading to chemoresistance of tumor cells is the increased activity of transporter proteins. The best-characterized transporter protein is MDR1/P-glycoprotein, and a number of clinical investigations have suggested that its intrinsic or acquired overexpression resulted in a poor clinical outcome of chemotherapy. Various types of compounds and techniques for the reversal of MDR1/P-glycoproteinmediated MDR have been developed, and efforts have concentrated on the inhibition of function and suppression of expression. This review summarizes the current state of knowledge of MDR1/P-glycoprotein and the modulation of MDR by targeting MDR1/P-glycoprotein.
Keywords: P-glycoprotein, crosslinking, transmembrane domain, protein-coding sequence, leukemia, SNP, MDR modulators
Current Pharmaceutical Design
Title: An Update on Overcoming MDR1-Mediated Multidrug Resistance in Cancer Chemotherapy
Volume: 12 Issue: 3
Author(s): Kohji Takara, Toshiyuki Sakaeda and Katsuhiko Okumura
Affiliation:
Keywords: P-glycoprotein, crosslinking, transmembrane domain, protein-coding sequence, leukemia, SNP, MDR modulators
Abstract: The intrinsic or acquired resistance to anticancer drugs remains one of the most significant factors impeding the progress of cancer chemotherapy. This phenomenon often involves simultaneous resistance to other anticancer drugs that differ in their chemical structure and mode of action and are not even used in chemotherapy. This phenotype has been called multidrug resistance (MDR). Although the cellular basis underlying MDR is not fully understood, several factors mediating therapy resistance in tumors have been proposed. One of the mechanisms leading to chemoresistance of tumor cells is the increased activity of transporter proteins. The best-characterized transporter protein is MDR1/P-glycoprotein, and a number of clinical investigations have suggested that its intrinsic or acquired overexpression resulted in a poor clinical outcome of chemotherapy. Various types of compounds and techniques for the reversal of MDR1/P-glycoproteinmediated MDR have been developed, and efforts have concentrated on the inhibition of function and suppression of expression. This review summarizes the current state of knowledge of MDR1/P-glycoprotein and the modulation of MDR by targeting MDR1/P-glycoprotein.
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Cite this article as:
Takara Kohji, Sakaeda Toshiyuki and Okumura Katsuhiko, An Update on Overcoming MDR1-Mediated Multidrug Resistance in Cancer Chemotherapy, Current Pharmaceutical Design 2006; 12 (3) . https://dx.doi.org/10.2174/138161206775201965
DOI https://dx.doi.org/10.2174/138161206775201965 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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