{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:36:36Z","timestamp":1790685396152,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100012869","name":"Morgan Adams Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009141","name":"Cancer League of Colorado","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1NS086956"],"award-info":[{"award-number":["RO1NS086956"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Group 3 medulloblastoma (MB) is often accompanied by MYC amplification. PLK1 is an oncogenic kinase that controls cell cycle and proliferation and has been preclinically validated as a cancer therapeutic target. Onvansertib (PCM-075) is a novel, orally available PLK1 inhibitor, which shows tumor growth inhibition in various types of cancer. We aim to explore the effect of onvansertib on MYC-driven medulloblastoma as a monotherapy or in combination with radiation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Crisper-Cas9 screen was used to discover essential genes for MB tumor growth. Microarray and immunohistochemistry on pediatric patient samples were performed to examine the expression of PLK1. The effect of onvansertib in vitro was measure by cell viability, colony-forming assays, extreme limiting dilution assay, and RNA-Seq. ALDH activity, cell-cycle distribution, and apoptosis were analyzed by flow cytometry. DNA damage was assessed by immunofluorescence staining. Medulloblastoma xenografts were generated to explore the monotherapy or radio-sensitizing effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PLK1 is overexpressed in Group 3 MB. The IC50 concentrations of onvansertib in Group 3 MB cell lines were in a low nanomolar range. Onvansertib reduced colony formation, cell proliferation, stem cell renewal and induced G2\/M arrest in vitro. Moreover, onvansertib in combination with radiation increased DNA damage and apoptosis compared with radiation treatment alone. The combination radiotherapy resulted in marked tumor regression in xenografts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings demonstrate the efficacy of a novel PLK1 inhibitor onvansertib in vitro and in xenografts of Group 3 MB, which suggests onvansertib is an effective strategy as monotherapy or in combination with radiotherapy in MB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noab207","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T16:01:32Z","timestamp":1630944092000},"page":"414-426","source":"Crossref","is-referenced-by-count":42,"title":["A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy"],"prefix":"10.1093","volume":"24","author":[{"given":"Dong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Veo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Fosmire","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Madhavan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilango","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Donson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Alimova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Linda Crnic Institute for Down Syndrome, Department of Pediatrics, Section of Developmental Biology, Children\u2019s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molishree","family":"Joshi","sequence":"additional","affiliation":[{"name":"Functional Genomics Facility, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Erlander","sequence":"additional","affiliation":[{"name":"Cardiff Oncology Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Ridinger","sequence":"additional","affiliation":[{"name":"Cardiff Oncology Inc., San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K","family":"Foreman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado, Aurora, Colorado, USA"},{"name":"Department of Neurosurgery, University of Colorado Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Vibhakar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado, Aurora, Colorado, USA"},{"name":"Department of Neurosurgery, University of 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