{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:45:57Z","timestamp":1784727957321,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["EIA-2017-020"],"award-info":[{"award-number":["EIA-2017-020"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["18\/RI\/5702"],"award-info":[{"award-number":["18\/RI\/5702"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Comprehensive Molecular Analytical Platform","award":["EIA-2017-020"],"award-info":[{"award-number":["EIA-2017-020"]}]},{"name":"The Comprehensive Molecular Analytical Platform","award":["18\/RI\/5702"],"award-info":[{"award-number":["18\/RI\/5702"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resistance to neoadjuvant chemoradiation therapy is a significant clinical challenge in the management of rectal cancer. There is an unmet need to identify the underlying mechanisms of treatment resistance to enable the development of biomarkers predictive of response and novel treatment strategies to improve therapeutic response. In this study, an in vitro model of inherently radioresistant rectal cancer was identified and characterized to identify mechanisms underlying radioresistance in rectal cancer. Transcriptomic and functional analysis demonstrated significant alterations in multiple molecular pathways, including the cell cycle, DNA repair efficiency and upregulation of oxidative phosphorylation-related genes in radioresistant SW837 rectal cancer cells. Real-time metabolic profiling demonstrated decreased reliance on glycolysis and enhanced mitochondrial spare respiratory capacity in radioresistant SW837 cells when compared to radiosensitive HCT116 cells. Metabolomic profiling of pre-treatment serum samples from rectal cancer patients (n = 52) identified 16 metabolites significantly associated with subsequent pathological response to neoadjuvant chemoradiation therapy. Thirteen of these metabolites were also significantly associated with overall survival. This study demonstrates, for the first time, a role for metabolic reprograming in the radioresistance of rectal cancer in vitro and highlights a potential role for altered metabolites as novel circulating predictive markers of treatment response in rectal cancer patients.<\/jats:p>","DOI":"10.3390\/ijms24087082","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:57:08Z","timestamp":1681268228000},"page":"7082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Energy Metabolism Is Altered in Radioresistant Rectal Cancer"],"prefix":"10.3390","volume":"24","author":[{"given":"Cro\u00ed E.","family":"Buckley","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine, Trinity Translational Medicine Institute, Trinity St James\u2019s Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Yin","sequence":"additional","affiliation":[{"name":"UCD School of Agriculture and Food Science, UCD Institute of Food and Health, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-3927","authenticated-orcid":false,"given":"Sebastian","family":"Meltzer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-3223","authenticated-orcid":false,"given":"Anne Hansen","family":"Ree","sequence":"additional","affiliation":[{"name":"Department of Oncology, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-4632","authenticated-orcid":false,"given":"Kathrine R\u00f8e","family":"Redalen","sequence":"additional","affiliation":[{"name":"Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-7499","authenticated-orcid":false,"given":"Lorraine","family":"Brennan","sequence":"additional","affiliation":[{"name":"UCD School of Agriculture and Food Science, UCD Institute of Food and Health, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacintha","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, Trinity Translational Medicine Institute, Trinity St James\u2019s Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Lynam-Lennon","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, Trinity Translational Medicine Institute, Trinity St James\u2019s Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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