Acidosis and cancer: from mechanism to neutralization

Cancer Metastasis Reviews
Arig Ibrahim-Hashim, Veronica Estrella

Abstract

The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been shown to inhibit local invasion and metastasis and improve immune surveillance in a variety of cancer model systems. This review will revisit the causes and consequences of acidosis by summarizing strategies used by cancer cells to adapt to acidosis, and how this acidity associated with carcinogenesis, metastasis, and immune function. Finally, this review will discuss how neutralization of acidity can be used to inhibit carcinogenesis and metastasis and improve anti-cancer immunotherapy.

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Citations

Mar 27, 2020·Gastroenterology Research and Practice·Wenjie LiHong Zhu
Aug 23, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xuewen QianFeihu Chen
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Jul 15, 2020·Kidney & Blood Pressure Research·Igor MatyukhinDaniel Patschan

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Clinical Trials Mentioned

NCT01198821
NCT01846429

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