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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 1/2014

Open Access 01-03-2014 | NON-THEMATIC REVIEW

Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R’s through dietary manipulation

Authors: Rainer J. Klement, Colin E. Champ

Published in: Cancer and Metastasis Reviews | Issue 1/2014

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Abstract

Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. We review the possible roles for calorie restriction (CR) and very low carbohydrate ketogenic diets (KDs) in modulating the five R’s of radiotherapy to improve the therapeutic window between tumor control and normal tissue complication probability. Important mechanisms we discuss include (1) improved DNA repair in normal, but not tumor cells; (2) inhibition of tumor cell repopulation through modulation of the PI3K–Akt–mTORC1 pathway downstream of insulin and IGF1; (3) redistribution of normal cells into more radioresistant phases of the cell cycle; (4) normalization of the tumor vasculature by targeting hypoxia-inducible factor-1α downstream of the PI3K–Akt–mTOR pathway; (5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. These mechanisms are discussed in the framework of animal and human studies, taking into account the commonalities and differences between CR and KDs. We conclude that CR and KDs may act synergistically with radiation therapy for the treatment of cancer patients and provide some guidelines for implementing these dietary interventions into clinical practice.
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Metadata
Title
Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R’s through dietary manipulation
Authors
Rainer J. Klement
Colin E. Champ
Publication date
01-03-2014
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 1/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-014-9495-3

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