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Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance

1
Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA
2
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 1026; https://doi.org/10.3390/cancers11071026
Received: 21 June 2019 / Revised: 17 July 2019 / Accepted: 18 July 2019 / Published: 20 July 2019
(This article belongs to the Special Issue Metastatic Progression and Tumour Heterogeneity)
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Abstract

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity. View Full-Text
Keywords: tumor microenvironment; interstitial pH; acidosis; tumor heterogeneity; magnetic resonance imaging; hyperpolarized 13C MRI; carbonic anhydrase; lactic acid; positron emission tomography tumor microenvironment; interstitial pH; acidosis; tumor heterogeneity; magnetic resonance imaging; hyperpolarized 13C MRI; carbonic anhydrase; lactic acid; positron emission tomography
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Korenchan, D.E.; Flavell, R.R. Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance. Cancers 2019, 11, 1026.

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