S2563
Radiobiology – Normal tissue radiobiology
ESTRO 2026
for RP model (Fig. 2a). As shown in Fig. 2b, Hmgcs2 knockout mice exhibited exacerbated colonic damage compared to wild-type controls, which was accompanied by reduced expression of tight junction proteins (ZO-1, Occludin) and the mucin MUC2. KEGG pathway enrichment analysis of distal colorectal tissues from WT and Hmgcs2 mice identified the top 20 enriched gene sets. Notably, the ferroptosis pathway was significantly altered, suggesting that HMGCS2 deficiency disrupts colorectal mucosal homeostasis by promoting ferroptosis and severe oxidative stress(Fig. 2c).
Conclusion: This study establishes that a ketogenic diet alleviates radiation proctitis and identifies HMGCS2 as a key mediator of this protective effect. Our findings highlight the therapeutic potential of targeting the HMGCS2 pathway through dietary interventions for radiation-induced intestinal injury. References: 1 Lenz, L., Rohr, R., Nakao, F., Libera, E. & Ferrari, A. Chronic radiation proctopathy: A practical review of endoscopic treatment. World J Gastrointest Surg 8, 151-160 (2016). https://doi.org/10.4240/wjgs.v8.i2.1512 Ross, F. C. et al. The interplay between diet and the gut microbiome: implications for health and disease. Nat Rev Microbiol 22, 671-686 (2024). https://doi.org/10.1038/s41579-024-01068-43 Dmitrieva-Posocco, O. et al. beta-Hydroxybutyrate suppresses colorectal cancer. Nature 605, 160-165 (2022). https://doi.org/10.1038/s41586-022-04649-64 Lu, W. et al. Platelet-derived growth factor C signaling is a potential therapeutic target for radiation proctopathy. Sci Transl Med 13 (2021). https://doi.org/10.1126/scitranslmed.abc2344 Keywords: radiation proctitis, Ketogenic diet, HMGCS2
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