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Cited by 566

The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.

Drug Resistance and Cellular Adaptation to Tumor Acidic pH Microenvironment

Open access
Wojtkowiak, Jonathan W., Verduzco, Daniel, Schramm, Karla J., Gillies, Robert J.·2011·Molecular Pharmaceutics
DOI 10.1021/mp200292c
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Abstract

Despite advances in developing novel therapeutic strategies, a major factor underlying cancer related death remains resistance to therapy. In addition to biochemical resistance, mediated by xenobiotic transporters or binding site mutations, resistance can be physiological, emerging as a consequence of the tumor's physical microenvironment. This review focuses on extracellular acidosis, an end result of high glycolytic flux and poor vascular perfusion. Low extracellular pH, pHe, forms a physiological drug barrier described by an "ion trapping" phenomenon. We describe how the acid-outside plasmalemmal pH gradient negatively impacts drug efficacy of weak base chemotherapies but is better suited for weakly acidic therapeutics. We will also explore the physiologic changes tumor cells undergo in response to extracellular acidosis which contribute to drug resistance including reduced apoptotic potential, genetic alterations, and elevated activity of a multidrug transporter, p-glycoprotein, pGP. Since low pHe is a hallmark of solid tumors, therapeutic strategies designed to overcome or exploit this condition can be developed.

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Metadata

Authors
Wojtkowiak, J. W., Verduzco, D., Schramm, K. J., & Gillies, R. J.
Venue
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Published
2011-10-26
Volume
8
Issue
6
Pages
2032-2038
ISSN
  • 1543-8384 (ISSN-L)
  • 1543-8392
DOI
10.1021/mp200292c
OpenAlex
W2092647316
Cited by
566
References
67
FWCI
8.13
Type
journal article
Language
en
Open access
green

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.