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Review
. 2022 Feb;61(2):200-224.
doi: 10.1002/mc.23379. Epub 2021 Dec 27.

Metabolic response to radiation therapy in cancer

Graham H Read  1 , Justine Bailleul  1 , Erina Vlashi  1   2 , Aparna H Kesarwala  3
Affiliations
Review

Metabolic response to radiation therapy in cancer

Graham H Read et al. Mol Carcinog. 2022 Feb.

Abstract

Tumor metabolism has emerged as a hallmark of cancer and is involved in carcinogenesis and tumor growth. Reprogramming of tumor metabolism is necessary for cancer cells to sustain high proliferation rates and enhanced demands for nutrients. Recent studies suggest that metabolic plasticity in cancer cells can decrease the efficacy of anticancer therapies by enhancing antioxidant defenses and DNA repair mechanisms. Studying radiation-induced metabolic changes will lead to a better understanding of radiation response mechanisms as well as the identification of new therapeutic targets, but there are few robust studies characterizing the metabolic changes induced by radiation therapy in cancer. In this review, we will highlight studies that provide information on the metabolic changes induced by radiation and oxidative stress in cancer cells and the associated underlying mechanisms.

Keywords: cancer; metabolism; oxidative stress; radiation therapy; radiosensitivity.

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Figures

Figure 1.
Figure 1.. A summary of methods for the study of cancer cell metabolism and its alterations after radiation.
Methods are grouped by their utility in vivo or in vitro, with suggested applications listed in blue boxes. Created with BioRender.com.
Figure 2.
Figure 2.. Radiation increases glucose metabolism to enhance antioxidant production and nucleic acid synthesis.
Ionizing radiation (yellow arrows) decreases PKM2 activity (in green) while increasing GLUT1-mediated glucose uptake and MCT-mediated exchange of pyruvate and lactate (in red), providing intermediates for nucleic acid synthesis and antioxidant production. Created with BioRender.com.
Figure 3.
Figure 3.. Radiation affects the lactate to pyruvate ratio via MCT transporters.
Ionizing radiation (yellow arrows) activates several pathways (indicated by red arrows) implicated in lactate production and transport. Created with BioRender.com.
Figure 4.
Figure 4.. Effects of radiation on amino acids and one-carbon metabolism.
Ionizing radiation (yellow arrows) affects expression of several pathways (in red text) associated with amino acid synthesis and redox metabolism. Other important signaling pathways that provide intermediates for these reactions are also shown. Created with BioRender.com.
Figure 5.
Figure 5.. Ionizing radiation affects fatty acid and lipid metabolism.
Ionizing radiation affects several pathways associated with the synthesis of cholesterol, fatty acids, and ceramides. Created with BioRender.com.
See this image and copyright information in PMC

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