{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:13:25Z","timestamp":1775736805041,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014461","name":"NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust\/Institute of Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014461","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015999","name":"Oracle Cancer Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015999","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016916","name":"Royal Marsden Cancer Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient\u2010derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common\n                    <jats:italic>MYB<\/jats:italic>\n                    ::\n                    <jats:italic>NFIB<\/jats:italic>\n                    or\n                    <jats:italic>MYBL1<\/jats:italic>\n                    ::\n                    <jats:italic>NFIB<\/jats:italic>\n                    translocations. We have developed the conditions for the generation of both 2D and 3D tumour organoid patient\u2010derived ACC models that retain MYB expression and can be used for drug studies. Using these models, we show\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    sensitivity of ACC cells to the bromodomain degrader, dBET6. Molecular studies show a decrease in BRD4 and MYB protein levels and target gene expression with treatment. The most prominent effect of dBET6 on tumours\n                    <jats:italic>in vivo<\/jats:italic>\n                    was a change in the relative composition of ACC cell types expressing either myoepithelial or ductal markers. We show that dBET6 inhibits the progenitor function of ACC cells, particularly in the myoepithelial marker\u2010expressing population, revealing a cell\u2010type\u2010specific sensitivity. These studies uncover a novel mechanistic effect of bromodomain inhibitors on tumours and highlight the need to impact both cell\u2010type populations for more effective treatments in ACC patients. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6209","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T13:00:55Z","timestamp":1696424455000},"page":"37-49","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cell\u2010type\u2010specific tumour sensitivity identified with a bromodomain targeting\n                    <scp>PROTAC<\/scp>\n                    in adenoid cystic carcinoma"],"prefix":"10.1002","volume":"262","author":[{"given":"Alexandra J","family":"Rose","sequence":"first","affiliation":[{"name":"Division of Cancer Biology Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4347-843X","authenticated-orcid":false,"given":"Mercedes M","family":"Fleming","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-5749","authenticated-orcid":false,"given":"Jeffrey C","family":"Francis","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Ning","sequence":"additional","affiliation":[{"name":"Tumour Modelling Facility Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Patrikeev","sequence":"additional","affiliation":[{"name":"Genomics Facility Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Genomics Facility Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J","family":"Harrington","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-1608","authenticated-orcid":false,"given":"Amanda","family":"Swain","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Institute of Cancer Research  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27408"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.125.2.149"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.10380"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2011.12.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23925"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69070"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2643"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2867-T"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67201"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128227"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909114106"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3502"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180939"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2016.03.001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.10.007"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2011.04.020"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006040"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0690"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0001"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.105"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0007-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.07.050"},{"key":"e_1_2_8_24_1","unstructured":"Illumina.Casava 1.8.2 San Diego 2013. 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