{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:05:49Z","timestamp":1791353149615,"version":"4.3.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The alternative lengthening of telomeres (ALT) pathway is a telomere maintenance mechanism that is driven by formation of DNA double-strand breaks at telomeres. ALT-positive malignancies often have mutational deletion of ATRX, but formation of DNA-protein complexes (DPCs) and elevated reactive oxygen species (ROS) also play a role in the induction of the ALT pathway. It has been recognised that excessive ALT activation can lead to rapid cell death, due to genome instability. Our objectives were to assess whether combining ROS-forming and DPC-forming treatments had a synergistic effect in ATRX-deficient cells. We found that SOD1 silencing was an effective method for inducing cell death in ATRX-deficient osteosarcoma cell lines; further, this approach was more effective in ATRX-null HeLa-LT than ATRX-wildtype cells. We also observed that dual treatment with DPC-forming chemotherapy (camptothecin) and SOD1 silencing led to a significantly higher level of DPCs, as well as signs of ALT pathway overactivity. Finally, our investigation demonstrated that pre-treatment of ATRX-null cells with shSOD1 significantly increased cellular sensitivity to camptothecin, with synergy between the two treatments. This research provides critical understanding to inform new treatment approaches\u2014which might eventually improve survival for affected individuals, and reduce long-term effects, for survivors of ALT-positive malignancies.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf118","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:41:56Z","timestamp":1751355716000},"page":"1638-1647","source":"Crossref","is-referenced-by-count":2,"title":["Silencing of <i>SOD1<\/i> sensitises <i>ATRX<\/i>-deficient cells to camptothecin treatment through increased activity of the alternative lengthening of telomeres pathway"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5364-8159","authenticated-orcid":false,"given":"Natalie","family":"Mattis","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headley Way , Oxford , OX3 9DU,","place":["United Kingdom"]},{"name":"Department of Biomedical Sciences, Oxford Brookes University , Gipsy Lane, Oxford , OX3 0BP,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headley Way , Oxford , OX3 9DU,","place":["United Kingdom"]},{"name":"MRC Weatherall Institute of Molecule Medicine, University of Oxford , Headley Way, Oxford , OX3 9DU,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanggeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive , Oxford , OX3 7DQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2335-3146","authenticated-orcid":false,"given":"Ester M","family":"Hammond","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive , Oxford , OX3 7DQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-6925","authenticated-orcid":false,"given":"Anna M","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headley Way , Oxford , OX3 9DU,","place":["United Kingdom"]},{"name":"MRC Weatherall Institute of Molecule Medicine, University of Oxford , Headley Way, Oxford , OX3 9DU,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"2025091922534355000_ref1","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.3390\/cancers13102384","article-title":"ALT positivity in human cancers: prevalence and clinical 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