The role of proton dynamics in the development and maintenance of multidrug resistance in cancer
With a projected 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm in 2015, improving treatment is an essential focus of cancer research today. Multi-drug resistance (MDR) is the leading cause of chemotherapeutic failure in the treatment of cancer, the term denoting a...
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Elsevier
2013
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| Online Access: | https://eprints.nottingham.ac.uk/2531/ |
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| author | Daniel, Chloë Bell, Charlotte Burton, Christopher Harguindey, Salvador Reshkinc, Stephan J. Rauch, Cyril |
| author_facet | Daniel, Chloë Bell, Charlotte Burton, Christopher Harguindey, Salvador Reshkinc, Stephan J. Rauch, Cyril |
| author_sort | Daniel, Chloë |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | With a projected 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm in 2015, improving treatment is an essential focus of cancer research today. Multi-drug resistance (MDR) is the leading cause of chemotherapeutic failure in the treatment of cancer, the term denoting a characteristic of the disease-causing agent to avoid damage by drugs designed to bring about their destruction. MDR is also characterised by a reversal of the pH gradient across cell membranes leading to an acidification of the outer milieu and an alkalinisation of the cytosol that is maintained by the proton pump vacuolar-type ATPase (V-ATPase) and the proton transporters: Na+/H+ exchanger (NHE1), Monocarboxylate Transporters (MCTs), Carbonic anhydrases (CAs) (mainly CA-IX), adenosinetriphosphate synthase, Na+/HCO3− co-transporter and the Cl−/HCO3−exchanger. This review aims to give an introduction to MDR. It will begin with an explanation for what MDR actually is and go on to look at the proposed mechanisms by which a state of drug resistance is achieved. The role of proton-pumps in creating an acidic extracellular pH and alkaline cytosol, as well as key biomechanical processes within the cell membrane itself, will be used to explain how drug resistance can be sustained. |
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| format | Article |
| id | nottingham-2531 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T18:18:31Z |
| publishDate | 2013 |
| publisher | Elsevier |
| recordtype | eprints |
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| spelling | nottingham-25312020-05-04T20:19:15Z https://eprints.nottingham.ac.uk/2531/ The role of proton dynamics in the development and maintenance of multidrug resistance in cancer Daniel, Chloë Bell, Charlotte Burton, Christopher Harguindey, Salvador Reshkinc, Stephan J. Rauch, Cyril With a projected 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm in 2015, improving treatment is an essential focus of cancer research today. Multi-drug resistance (MDR) is the leading cause of chemotherapeutic failure in the treatment of cancer, the term denoting a characteristic of the disease-causing agent to avoid damage by drugs designed to bring about their destruction. MDR is also characterised by a reversal of the pH gradient across cell membranes leading to an acidification of the outer milieu and an alkalinisation of the cytosol that is maintained by the proton pump vacuolar-type ATPase (V-ATPase) and the proton transporters: Na+/H+ exchanger (NHE1), Monocarboxylate Transporters (MCTs), Carbonic anhydrases (CAs) (mainly CA-IX), adenosinetriphosphate synthase, Na+/HCO3− co-transporter and the Cl−/HCO3−exchanger. This review aims to give an introduction to MDR. It will begin with an explanation for what MDR actually is and go on to look at the proposed mechanisms by which a state of drug resistance is achieved. The role of proton-pumps in creating an acidic extracellular pH and alkaline cytosol, as well as key biomechanical processes within the cell membrane itself, will be used to explain how drug resistance can be sustained. Elsevier 2013-05 Article PeerReviewed Daniel, Chloë, Bell, Charlotte, Burton, Christopher, Harguindey, Salvador, Reshkinc, Stephan J. and Rauch, Cyril (2013) The role of proton dynamics in the development and maintenance of multidrug resistance in cancer. BBA - Biochimica et Biophysica Acta, 1832 (5). pp. 606-617. ISSN 0006-3002 Multidrug resistance; Proton pump; Cancer; Drug efflux; Membrane physical biology http://www.sciencedirect.com/science/article/pii/S0925443913000343 doi:10.1016/j.bbadis.2013.01.020 doi:10.1016/j.bbadis.2013.01.020 |
| spellingShingle | Multidrug resistance; Proton pump; Cancer; Drug efflux; Membrane physical biology Daniel, Chloë Bell, Charlotte Burton, Christopher Harguindey, Salvador Reshkinc, Stephan J. Rauch, Cyril The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title | The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title_full | The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title_fullStr | The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title_full_unstemmed | The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title_short | The role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| title_sort | role of proton dynamics in the development and maintenance of multidrug resistance in cancer |
| topic | Multidrug resistance; Proton pump; Cancer; Drug efflux; Membrane physical biology |
| url | https://eprints.nottingham.ac.uk/2531/ https://eprints.nottingham.ac.uk/2531/ https://eprints.nottingham.ac.uk/2531/ |