{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:57:59Z","timestamp":1753891079881,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Metastatic prostate cancer (PCa) poses a significant public health concern. While radiation therapy (RT) is commonly utilized in the treatment of synchronous oligometastatic hormone sensitive prostate cancer (OM-HSPC), the occurrence of biochemical recurrence still remains. To deepen our understanding and optimize the outcome of OM-HSPC, we conducted this study to investigate the characteristics of PCa progression and explore potential synergistic mechanisms involving carbon-ion radiotherapy (CIRT) and neoadjuvant androgen deprivation treatment (naADT) in OM-HSPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Metabolomic analysis was conducted with 72 urinary samples (at different timepoints) from 33 Patients (T2-3N0M0-1b) and 18 healthy volunteers by using liquid chromatography-tandem mass spectrometry (LC-MS\/MS). MetaboAnalyst website and R software were employed for metabolomic analysis and visualization (using the criteria of <jats:italic>p<\/jats:italic> value &amp;lt; 0.05 and |FC|&amp;gt;1.5). The impact of CIRT on metabolism were further verified and explored through <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that most metabolites (223 out of 233) were upregulated in treatment-na\u00efve PCa samples compared to healthy samples. After naADT, 60 core risk metabolites were still significantly related to PCa\u2019s progression, and the glutamine level which was significantly higher in OM-HSPC compared to other groups. Remarkably, after CIRT treatment, the glutamine levels in OM-HSPC were significantly reduced to the level of healthy samples. Experiments further confirmed CIRT\u2019s ability to suppress glutamine levels in PCa tumors and its potential enhancement with glutamine deprivation intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CIRT with naADT might synergistically inhibit HS-OMPC development, progression and even the ADT resistance through glutamine metabolism repression, moreover, the glutamine metabolism might be a novel target to further improved the efficacy of CIRT.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1291653","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T04:55:25Z","timestamp":1699937725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The metabolic repression effect of carbon-ion radiotherapy in synchronous hormone-sensitive oligometastatic prostate 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