The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Falcone, M., Uribe, A., H. et al. Br J Cancer. 127: 1773–1786. (2022).
doi: 0.1038/s41416-022-01965-6.
Summary of the findings
About 50% of all cancer patients are treated with radiotherapy at some stage of their disease. This directly damages DNA and generates radiation-induced reactive oxygen species (ROS), causing further oxidative damage. Boosting both of these processes establishes the backbone of radiotherapy resistance. However, the metabolic mechanisms have been poorly characterised.
The non-essential amino acid Serine and Glycine (SG) are the major contributors of carbon and nitrogen units for nucleotide and glutathione synthesis – the main cellular antioxidant. Dietary limitation of SG in several cancer models has shown exceptional results, especially in combination with standard therapies. Thus, we sought to investigate the impact of SG restriction on radiotherapy.
We show a dramatic dose and time-dependent metabolic response to radiation in various cancers. In addition to predicted metabolic rewirings (e.g. nucleotides and glutathione synthesis), we unexpectedly found a consistent increase of Krebs cycle intermediates. We demonstrated that SG starvation could prevent this upregulation, making this pathway a significant component in cancer cells’ metabolic response to radiotherapy. Our results corroborate prior works demonstrating the sensitising effect of mitochondrial inhibition. Altogether we highlight the potential of combining dietary nutrient modulation with standard cancer therapy as a means of sensitisation.
Future impact
This study explored the metabolic response to radiotherapy. We suggest combining dietary limitations of the non-essential amino acid serine and glycine SG as a potentially effective strategy to sensitise a range of common cancers to radiotherapy. Amino acid-restricted diets are now beginning to enter clinical trials making this study highly relevant. Establishing the pre-clinical efficacy of sensitising adjuvants in multiple tumour types is the answer to a pressing clinical need.
