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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

Authors

Ziad Omran

Paula Scaife

Simon Stewart



Abstract

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.

Citation

Omran, Z., Scaife, P., Stewart, S., & Rauch, C. (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, https://doi.org/10.1016/j.semcancer.2017.01.002

Journal Article Type Article
Acceptance Date Jan 5, 2017
Online Publication Date Jan 8, 2017
Publication Date Apr 1, 2017
Deposit Date Jan 11, 2017
Publicly Available Date Jan 11, 2017
Journal Seminars in Cancer Biology
Print ISSN 1044-579X
Electronic ISSN 1096-3650
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 43
DOI https://doi.org/10.1016/j.semcancer.2017.01.002
Keywords Pharmacokinetic; Drug transporter; Membrane biophysics; Warburg effect
Public URL http://eprints.nottingham.ac.uk/id/eprint/39780
Publisher URL http://www.sciencedirect.com/science/article/pii/S1044579X17300020
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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