期刊
SEMINARS IN CANCER BIOLOGY
卷 43, 期 -, 页码 42-48出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2017.01.002
关键词
Pharmacokinetic; Drug transporter; Membrane biophysics; Warburg effect
类别
资金
- University of Nottingham
- Biological and Biophysical Scientific Research Council of United kingdom
- Vertex Pharmaceuticals
- King Abdulaziz City for Sciences and Technology, Saudi Arabia [13-MED2515-10, 14-MED1472-10]
The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
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