{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:16:00Z","timestamp":1790345760038,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Noncommunicable Chronic Diseases"},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0525300"],"award-info":[{"award-number":["2024ZD0525300"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Science and Technology Plan Project","doi-asserted-by":"publisher","award":["24JCZDJC00180"],"award-info":[{"award-number":["24JCZDJC00180"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFC2510000"],"award-info":[{"award-number":["2023YFC2510000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>AbstractAbstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite advances in small-molecule inhibitors (SMIs), the clinical outcomes for glioblastoma (GBM) remain bleak. Recently, polymerase I and transcript release factor (PTRF\/Cavin1) has emerged as a promising therapeutic target, with its inhibitor EPIC-1042 demonstrating preclinical antitumor activity. However, the therapeutic limitations of SMIs necessitate alternative strategies to achieve enduring target suppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EPIC-0726, a proteolysis-targeting chimera (PROTAC) degrader of PTRF, was developed through computer-aided drug design (CADD). Target engagement and degradation specificity were validated by Western blot. Quantitative proteomics identified downstream effectors, while mechanistic insights were elucidated through co-immunoprecipitation, immunofluorescence, and ubiquitination profiling. Orthotopic GBM models were used to assess therapeutic efficacy and temozolomide (TMZ) sensitization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EPIC-0726 induced dose-dependent PTRF degradation via the ubiquitin-proteasome system (UPS), requiring ternary complex formation. Proteomic analysis revealed RBX1, a core component of E3 ligase complexes, as a key downstream target. PTRF degradation by EPIC-0726 destabilized RBX1, concurrently suppressing K63-linked ubiquitination-mediated ERK1\/2\/AKT activation and stabilizing p21 via impaired K48-dependent proteasomal degradation. In vivo, EPIC-0726 monotherapy inhibited GBM growth and synergized with TMZ, with effects more potent than that of EPIC-1042.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes PROTAC-mediated PTRF degradation as a mechanistically distinct manner to activate proteolysis strategy-enhanced TMZ efficacy by ERK1\/2\/AKT kinase suppression and p21 stabilization (PEAKS) through the PTRF-RBX1 regulatory axis. The superior efficacy of EPIC-0726 over EPIC-1042, particularly in overcoming TMZ resistance, provides a paradigm-shifting therapeutic approach for GBM. Our findings warrant the clinical translation of EPIC-0726 as both a monotherapy and a backbone for combination regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf253","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T12:02:10Z","timestamp":1761307330000},"page":"597-612","source":"Crossref","is-referenced-by-count":3,"title":["PEAKS activation by PROTAC EPIC-0726 potentiates temozolomide in glioblastoma via K63\/K48 ubiquitination-dependent ERK\/AKT suppression and p21 stabilization"],"prefix":"10.1093","volume":"28","author":[{"given":"Biao","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoteng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China (J.Z.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eryan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China (E.Y.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixue","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China (S.Y.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longtao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3255-3369","authenticated-orcid":false,"given":"Chunsheng","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"},{"name":"Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (B.H., D.S, X.C., Q.W., Q.Z., J.J., Y.H., C.C., Y.D., H.X., L.C., Y.Z., X.Z., S.L., Y.L., C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"2026041216240937500_noaf253-B1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and other primary brain malignancies in adults","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"2026041216240937500_noaf253-B2","doi-asserted-by":"crossref","first-page":"188616","DOI":"10.1016\/j.bbcan.2021.188616","article-title":"Elucidating the mechanisms of temozolomide resistance in gliomas and the strategies to overcome the resistance","volume":"1876","author":"Tomar","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"2026041216240937500_noaf253-B3","doi-asserted-by":"crossref","first-page":"101896","DOI":"10.1016\/j.ctrv.2019.101896","article-title":"Molecular targeted therapy of glioblastoma","volume":"80","author":"Le Rhun","year":"2019","journal-title":"Cancer Treat Rev"},{"key":"2026041216240937500_noaf253-B4","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.addr.2021.01.012","article-title":"Frontiers in the treatment of glioblastoma: past, present and emerging","volume":"171","author":"Janjua","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"2026041216240937500_noaf253-B5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"Bekes","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"2026041216240937500_noaf253-B6","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1126\/science.aam7340","article-title":"Waste disposal\u2014an attractive strategy for cancer therapy","volume":"355","author":"Salami","year":"2017","journal-title":"Science"},{"key":"2026041216240937500_noaf253-B7","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1039\/D2CS00193D","article-title":"PROTACs: past, present and future","volume":"51","author":"Li","year":"2022","journal-title":"Chem Soc Rev"},{"key":"2026041216240937500_noaf253-B8","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1039\/D2CS00116K","article-title":"Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders","volume":"51","author":"Yamamoto","year":"2022","journal-title":"Chem Soc Rev"},{"key":"2026041216240937500_noaf253-B9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cell.2007.11.042","article-title":"PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function","volume":"132","author":"Hill","year":"2008","journal-title":"Cell"},{"key":"2026041216240937500_noaf253-B10","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.7150\/thno.22952","article-title":"The role of PTRF\/Cavin1 as a biomarker in both glioma and serum exosomes","volume":"8","author":"Huang","year":"2018","journal-title":"Theranostics"},{"key":"2026041216240937500_noaf253-B11","doi-asserted-by":"crossref","first-page":"6674","DOI":"10.7150\/thno.45688","article-title":"Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma","volume":"10","author":"Wang","year":"2020","journal-title":"Theranostics"},{"key":"2026041216240937500_noaf253-B12","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.7150\/thno.71763","article-title":"PTRF\/cavin-1 enhances chemo-resistance and promotes temozolomide efflux through extracellular vesicles in glioblastoma","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"2026041216240937500_noaf253-B13","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/neuonc\/noad159","article-title":"EPIC-1042 as a potent PTRF\/Cavin1-caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for glioblastoma","volume":"26","author":"Hong","year":"2024","journal-title":"Neuro Oncol"},{"key":"2026041216240937500_noaf253-B14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cell.2016.03.003","article-title":"Types of ubiquitin ligases","volume":"165","author":"Morreale","year":"2016","journal-title":"Cell"},{"key":"2026041216240937500_noaf253-B15","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/416703a","article-title":"Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex","volume":"416","author":"Zheng","year":"2002","journal-title":"Nature"},{"key":"2026041216240937500_noaf253-B16","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev.biochem.78.101807.093809","article-title":"RING domain E3 ubiquitin ligases","volume":"78","author":"Deshaies","year":"2009","journal-title":"Annu Rev Biochem"},{"key":"2026041216240937500_noaf253-B17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/cr.2016.39","article-title":"Ubiquitin modifications","volume":"26","author":"Swatek","year":"2016","journal-title":"Cell Res"},{"key":"2026041216240937500_noaf253-B18","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41420-022-01204-0","article-title":"Role of K63-linked ubiquitination in cancer","volume":"8","author":"Cao","year":"2022","journal-title":"Cell Death Discov"},{"key":"2026041216240937500_noaf253-B19","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature07385","article-title":"Comprehensive genomic characterization defines human Glioblastoma genes and core pathways","volume":"455","author":"The Cancer Genome Atlas Research Network","year":"2008","journal-title":"Nature"},{"key":"2026041216240937500_noaf253-B20","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/s41556-021-00732-8","article-title":"TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination","volume":"23","author":"Zhu","year":"2021","journal-title":"Nat Cell Biol"},{"key":"2026041216240937500_noaf253-B21","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1126\/science.1175065","article-title":"The E3 ligase TRAF6 regulates Akt ubiquitination and activation","volume":"325","author":"Yang","year":"2009","journal-title":"Science"},{"key":"2026041216240937500_noaf253-B22","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.cell.2012.02.065","article-title":"The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis","volume":"149","author":"Chan","year":"2012","journal-title":"Cell"},{"key":"2026041216240937500_noaf253-B23","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2019.06.004","article-title":"Molecular mechanisms of cereblon-based drugs","volume":"202","author":"Asatsuma-Okumura","year":"2019","journal-title":"Pharmacol Ther"},{"key":"2026041216240937500_noaf253-B24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cell.2007.12.021","article-title":"PTRF triggers a cave in","volume":"132","author":"Chadda","year":"2008","journal-title":"Cell"},{"key":"2026041216240937500_noaf253-B25","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/neuonc\/noac204","article-title":"EGFR, the Lazarus target for precision oncology in glioblastoma","volume":"24","author":"Lin","year":"2022","journal-title":"Neuro Oncol"},{"key":"2026041216240937500_noaf253-B26","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/cac2.12502","article-title":"Blockage of EGFR\/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma","volume":"43","author":"Cui","year":"2023","journal-title":"Cancer Commun (Lond)"},{"key":"2026041216240937500_noaf253-B27","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.molcel.2016.02.009","article-title":"Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis","volume":"61","author":"Li","year":"2016","journal-title":"Mol Cell"},{"key":"2026041216240937500_noaf253-B28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.molmed.2017.02.001","article-title":"p21: a two-faced genome guardian","volume":"23","author":"Georgakilas","year":"2017","journal-title":"Trends Mol Med"},{"key":"2026041216240937500_noaf253-B29","doi-asserted-by":"crossref","first-page":"25752","DOI":"10.1074\/jbc.M301774200","article-title":"Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase","volume":"278","author":"Bornstein","year":"2003","journal-title":"J Biol Chem"},{"key":"2026041216240937500_noaf253-B30","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.cell.2013.06.048","article-title":"Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression","volume":"154","author":"Chan","year":"2013","journal-title":"Cell"},{"key":"2026041216240937500_noaf253-B31","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: p53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ"},{"key":"2026041216240937500_noaf253-B32","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/neuonc\/noac242","article-title":"A novel compound EPIC-0412 reverses temozolomide resistance via inhibiting DNA repair\/MGMT in glioblastoma","volume":"25","author":"Zhao","year":"2023","journal-title":"Neuro Oncol"},{"key":"2026041216240937500_noaf253-B33","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41418-020-00696-6","article-title":"The role of E3 ubiquitin ligases in the development and progression of glioblastoma","volume":"28","author":"Humphreys","year":"2021","journal-title":"Cell Death Differ"},{"key":"2026041216240937500_noaf253-B34","doi-asserted-by":"crossref","first-page":"e202204395","DOI":"10.1002\/anie.202204395","article-title":"Discovery of a potent and selective degrader for USP7","volume":"61","author":"Pei","year":"2022","journal-title":"Angew Chem Int Ed Engl"},{"key":"2026041216240937500_noaf253-B35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1021\/acscentsci.0c00411","article-title":"Targeted degradation of oncogenic KRASG12C by VHL-recruiting PROTACs","volume":"6","author":"Bond","year":"2020","journal-title":"ACS Cent Sci"},{"key":"2026041216240937500_noaf253-B36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.chembiol.2017.09.010","article-title":"Lessons in PROTAC design from selective degradation with a promiscuous warhead","volume":"25","author":"Bondeson","year":"2018","journal-title":"Cell Chem Biol"},{"key":"2026041216240937500_noaf253-B37","doi-asserted-by":"crossref","first-page":"6685","DOI":"10.1021\/acs.jmedchem.8b00506","article-title":"Discovery of QCA570 as an exceptionally potent and efficacious proteolysis targeting chimera (PROTAC) degrader of the bromodomain and extra-terminal (BET) proteins capable of inducing complete and durable tumor regression","volume":"61","author":"Qin","year":"2018","journal-title":"J Med Chem"},{"key":"2026041216240937500_noaf253-B38","doi-asserted-by":"crossref","first-page":"14481","DOI":"10.1002\/anie.202003500","article-title":"Mutant-selective allosteric EGFR degraders are effective against a broad range of drug-resistant mutations","volume":"59","author":"Jang","year":"2020","journal-title":"Ang Chem Int Ed Engl"},{"key":"2026041216240937500_noaf253-B39","doi-asserted-by":"crossref","first-page":"103395","DOI":"10.1016\/j.drudis.2022.103395","article-title":"PROTAC technology: a new drug design for chemical biology with many challenges in drug discovery","volume":"28","author":"Guedeney","year":"2023","journal-title":"Drug Discov Today"},{"key":"2026041216240937500_noaf253-B40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nature16979","article-title":"Structural basis of lenalidomide-induced CK1\u03b1 degradation by the CRL4(CRBN) ubiquitin ligase","volume":"532","author":"Petzold","year":"2016","journal-title":"Nature"}],"container-title":["Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noaf253\/64956448\/noaf253.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/28\/3\/597\/64956448\/noaf253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/28\/3\/597\/64956448\/noaf253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T20:24:23Z","timestamp":1776025463000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article\/28\/3\/597\/8303920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,10,27]]},"published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/neuonc\/noaf253","relation":{},"ISSN":["1522-8517","1523-5866"],"issn-type":[{"value":"1522-8517","type":"print"},{"value":"1523-5866","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,10,27]]}}}