{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:50:38Z","timestamp":1780476638317,"version":"3.54.1"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["MOST107-2314-B-038-011, MOST107-2314-B-195-017-MY2, MOST 108-2314-B-038-061-MY3 and MOST108-2314-B-038-054-MY3"],"award-info":[{"award-number":["MOST107-2314-B-038-011, MOST107-2314-B-195-017-MY2, MOST 108-2314-B-038-061-MY3 and MOST108-2314-B-038-054-MY3"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pediatric ependymomas are a type of malignant brain tumor that occurs in children. The overall 10-year survival rate has been reported as being 45\u201375%. Maximal safe surgical resection combined with adjuvant chemoradiation therapy is associated with the highest overall and progression-free survival rates. Despite aggressive treatment, one-third of ependymomas exhibit recurrence within 2 years of initial treatment. Therefore, this study aimed to find new agents to overcome chemoresistance and defer radiotherapy treatment since, in addition, radiation exposure may cause long-term side effects in the developing brains of young children. By using integrated bioinformatics and through experimental validation, we found that at least one of the genes CCND1 and CDK4 is overexpressed in ependymomas. The use of abemaciclib, a highly selective CDK4\/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell-cycle-related and DNA-repair-related gene expression via the suppression of RB phosphorylation, which was determined through RNA-seq and Western blot analyses. Furthermore, abemaciclib effectively induced cell death in vitro. The efficiency of abemaciclib was validated in vivo using subcutaneously implanted ependymoma tissues from patient-derived xenografts (PDXs) in mouse models. Treatment with abemaciclib showed encouraging results in preclinical pediatric ependymoma models and represents a potential therapeutic strategy for treating challenging tumors in children.<\/jats:p>","DOI":"10.3390\/cancers12123597","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:06:09Z","timestamp":1606853169000},"page":"3597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Abemaciclib, A Selective CDK4\/6 Inhibitor, Restricts the Growth of Pediatric Ependymomas"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-9812","authenticated-orcid":false,"given":"Muh-Lii","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 104, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-466X","authenticated-orcid":false,"given":"Chun-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ru","family":"Liu","sequence":"additional","affiliation":[{"name":"Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Hsu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-6227","authenticated-orcid":false,"given":"Tai-Tong","family":"Wong","sequence":"additional","affiliation":[{"name":"Institutes of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Pediatric Neurosurgery, Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Neuroscience Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Pediatric Brain Tumor Program, Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8994-9452","authenticated-orcid":false,"given":"Sey-En","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, New Taipei Municipal Tucheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City 236, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing-Shiung","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurosurgery, Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Huei","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 104, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-9246","authenticated-orcid":false,"given":"Tsung-Han","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Neuroscience Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1002\/cncr.21430","article-title":"Primary pediatric brain tumors: Statistics of Taipei VGH, Taiwan (1975\u20132004)","volume":"104","author":"Wong","year":"2005","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.18632\/oncotarget.23509","article-title":"Significance of cyclin D1 overexpression in progression and radio-resistance 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