{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:56:33Z","timestamp":1785815793211,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Cure Starts Now Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma (DIPG), are highly aggressive tumors with dismal prognoses despite multimodal therapy including surgery, radiation therapy, and chemotherapy. To achieve cellular immortality cancer cells must overcome replicative senescence and apoptosis by activating telomere maintenance mechanisms (TMMs) through the reactivation of telomerase activity or using alternative lengthening of telomere (ALT) pathways. Although the ALT phenotype is more prevalent in pHGGs compared to adult HGGs, the molecular pathway and the prognostic significance of ALT activation are not well understood in pHGGs. Here, we report the heterogeneity of TMM in pHGGs and their association with genetic alterations. Additionally, we show that sensitivity to the protein kinase ataxia telangiectasia- and RAD3-related protein (ATR) inhibitor and the ATR downstream target CHK1 is not specific to pHGG ALT-positive cells. Together, these findings underscore the need for novel therapeutic strategies to target ALT in pHGG tumors.<\/jats:p>","DOI":"10.3390\/cancers15123070","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T01:38:41Z","timestamp":1686101921000},"page":"3070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alternative Lengthening of Telomeres in Pediatric High-Grade Glioma and Therapeutic Implications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4517-2255","authenticated-orcid":false,"given":"Banlanjo","family":"Umaru","sequence":"first","affiliation":[{"name":"Center for Childhood Cancer Research, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satarupa","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Senthil Kumar","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0564-0181","authenticated-orcid":false,"given":"Rachid","family":"Drissi","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/neuonc\/noq191","article-title":"Temozolomide in the treatment of high-grade gliomas in children: A report from the Children\u2019s Oncology Group","volume":"13","author":"Cohen","year":"2011","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"DeNunzio, N.J., and Yock, T.I. 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