{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:42:24Z","timestamp":1788172944808,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recurrent\/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed through an <jats:italic>MYB\u2010NFIB<\/jats:italic> rearrangement. The authors hypothesized that AKT inhibition with the allosteric inhibitor MK\u20102206 could decrease MYB expression and induce tumor regression in patients with incurable ACC (ClinicalTrials.gov identifier NCT01604772).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with progressive, incurable ACC were enrolled and received MK\u20102206 150\u00a0mg weekly; escalation to 200\u00a0mg was allowed. The primary end point was confirmed response. Secondary end points were progression\u2010free survival, overall survival, and safety. An exploratory analysis evaluating the effect of MK\u20102206 on MYB expression was conducted in a subset of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen patients were enrolled, and 14 were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease, and one had disease progression as their best response. The median progression\u2010free survival was 9.7\u00a0months (95% CI, 3.8\u201311.8 months), and the median overall survival was 18.0\u00a0months (95% CI, 11.8\u201329.9 months). Nine of 16 patients (56%) had at least one grade 3 treatment\u2010related adverse event, and the most common were rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) had detectable MYB expression by immunohistochemistry, and seven of 14 tumors (50%) had an <jats:italic>MYB\u2010NFIB<\/jats:italic> gene rearrangement. Serial biopsies revealed decreased MYB levels with MK\u20102206 in four of five patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MK\u20102206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, although the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35103","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T05:00:35Z","timestamp":1699592435000},"page":"702-712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A phase 2 study of MK\u20102206 in patients with incurable adenoid cystic carcinoma (Alliance A091104)"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-3742","authenticated-orcid":false,"given":"Alan L.","family":"Ho","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"},{"name":"Weill Cornell Medicine and New York Presbyterian Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R.","family":"Foster","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamprasad","family":"Deraje Vasudeva","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"},{"name":"Vasta Global  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Katabi","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina R.","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P.","family":"Frenette","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute Atrium Health  Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Pfister","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"},{"name":"Weill Cornell Medicine and New York Presbyterian Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Erlichman","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary K.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Case Comprehensive Cancer Center Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.125.2.149"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109610(97)00153\u20100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201021\u20101061"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32754"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.18.01859"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909114106"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3502"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.86"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201011\u20101870"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/pas.0b013e3182002777"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389\u2010021\u201000309\u2010y"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.cd\u201015\u20100859"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20102867\u2010T"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12984"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153691"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci128227"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2019.09.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx017"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180939"},{"issue":"3","key":"e_1_2_10_21_1","first-page":"773","article-title":"Establishment of patient\u2010derived xenograft models of adenoid cystic carcinoma to assess pre\u2010clinical efficacy of combination therapy of a PI3K inhibitor and retinoic acid","volume":"11","author":"Sun B","year":"2021","journal-title":"Am J Cancer Res"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m504703200"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.am2011\u2010638"},{"key":"e_1_2_10_24_1","volume-title":"MK\u20102206","author":"Merck & Company, Inc","year":"2008"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.35.5263"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201014\u20100868"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204345"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.15.11.5966"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201012\u20101319"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010045"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103745"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2017.03.002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.10.031"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080913"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.mct\u201013\u20100442\u2010t"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201015\u20102301"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.36.9678"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.017"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105366"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002618\u20106"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201020\u20101192"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2022.106028"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018\u20100515"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111743"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.35103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:39:15Z","timestamp":1760305155000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.35103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/cncr.35103"],"URL":"https:\/\/doi.org\/10.1002\/cncr.35103","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,10]]},"assertion":[{"value":"2023-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}