Abstract
Introduction
Radiotherapy is a mainstay of cancer treatment. Clinical studies revealed a heterogenous response to radiotherapy, from a complete response to even disease progression. To that end, finding the relative prognostic factors of disease outcomes and predictive factors of treatment efficacy and toxicity is essential. It has been demonstrated that radiation response depends on DNA damage response, cell cycle phase, oxygen concentration, and growth rate. Emerging evidence suggests that altered mitochondrial metabolism is associated with radioresistance.
Methods
This article provides a comprehensive evaluation of the role of mitochondria in radiotherapy efficacy and toxicity. In addition, it demonstrates how mitochondria might be involved in the famous 6Rs of radiobiology.
Results
In terms of this idea, decreasing the mitochondrial metabolism of cancer cells may increase radiation response, and enhancing the mitochondrial metabolism of normal cells may reduce radiation toxicity. Enhancing the normal cells (including immune cells) mitochondrial metabolism can potentially improve the tumor response by enhancing immune reactivation. Future studies are invited to examine the impacts of mitochondrial metabolism on radiation efficacy and toxicity.
Graphical abstract
Improving radiotherapy response with diminishing cancer cells’ mitochondrial metabolism, and reducing radiotherapy toxicity with enhancing normal cells’ mitochondrial metabolism.
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Data availability
N/A.
References
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Acknowledgements
We dedicate this article to the loving memory of our beloved mentor Moslem Bahadori, who was a pioneer in structuring the “National Council for Medical Education” and “National Organization for Educational Evaluation”, and a founder of the Iranian National Tuberculosis and Lung Diseases Research Center in Iran.
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Taghizadeh-Hesary, F., Houshyari, M. & Farhadi, M. Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity. J Cancer Res Clin Oncol 149, 6719–6741 (2023). https://doi.org/10.1007/s00432-023-04592-7
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DOI: https://doi.org/10.1007/s00432-023-04592-7