Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer

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 developm...

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Main Authors: Omran, Ziad, Scaife, Paula, Stewart, Simon, Rauch, Cyril
Format: Article
Published: Elsevier 2017
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Online Access:https://eprints.nottingham.ac.uk/39780/
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author Omran, Ziad
Scaife, Paula
Stewart, Simon
Rauch, Cyril
author_facet Omran, Ziad
Scaife, Paula
Stewart, Simon
Rauch, Cyril
author_sort Omran, Ziad
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-397802020-05-04T19:58:10Z https://eprints.nottingham.ac.uk/39780/ Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer Omran, Ziad Scaife, Paula Stewart, Simon Rauch, Cyril 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. Elsevier 2017-04 Article PeerReviewed Omran, Ziad, Scaife, Paula, Stewart, Simon and Rauch, Cyril (2017) Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer. Seminars in Cancer Biology, 43 . pp. 42-48. ISSN 1096-3650 Pharmacokinetic; Drug transporter; Membrane biophysics; Warburg effect http://www.sciencedirect.com/science/article/pii/S1044579X17300020 doi:10.1016/j.semcancer.2017.01.002 doi:10.1016/j.semcancer.2017.01.002
spellingShingle Pharmacokinetic; Drug transporter; Membrane biophysics; Warburg effect
Omran, Ziad
Scaife, Paula
Stewart, Simon
Rauch, Cyril
Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title_full Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title_fullStr Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title_full_unstemmed Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title_short Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer
title_sort physical and biological characteristics of multi drug resistance (mdr): an integral approach considering ph and drug resistance in cancer
topic Pharmacokinetic; Drug transporter; Membrane biophysics; Warburg effect
url https://eprints.nottingham.ac.uk/39780/
https://eprints.nottingham.ac.uk/39780/
https://eprints.nottingham.ac.uk/39780/