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Standard therapy involves surgery followed by radiation therapy. The majority of ACC has MYB overexpression and MYB\u2010NFIB gene fusions, while Notch mutations are associated with aggressive behavior. Targeted therapies against these drivers or their downstream targets have been incompletely explored, especially in combination with radiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>cBioPortal was used for genomic and survival analyses. MYB, AKT, ATR, NOTCH, and NFIB expression was assessed via RNA\u2010seq, qRT\u2010PCR, and western blot. Radiation sensitization was evaluated by clonogenic assays while the effect on DNA damage was tested using \u03b3H2AX and RAD51 foci assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MYB, ATR, AKT1, Notch1, Notch2, and NFIB are overexpressed in ACC tumors, PDX, and cell lines. ACC patients with ATR, AKT, MYB, and NFIB alterations have poor overall survival. ATR, AKT, and Notch inhibitors sensitized UM\u2010HACC2A cells to radiation. Drugs and radiation combination reduced target mRNA expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ATR, AKT, and Notch inhibitors radiosensitize a preclinical model of ACC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70253","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:44:29Z","timestamp":1775112269000},"page":"2364-2376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>AKT<\/scp>\n                    ,\n                    <scp>ATR<\/scp>\n                    , and Notch Inhibitors Radiosensitize a Preclinical Model of Adenoid Cystic Carcinoma"],"prefix":"10.1002","volume":"48","author":[{"given":"Shivani","family":"Thoidingjam","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmitha","family":"Sriramulu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya Haider","family":"Muratoglu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"},{"name":"Henry Ford Health + Michigan State University Health Sciences  Detroit Michigan USA"},{"name":"Department of Radiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oudai","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Movsas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Henry Ford Cancer Institute, Henry Ford Health  Detroit Michigan USA"},{"name":"Department of Radiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haythem","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Henry Ford Health  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Henry Ford Health  Detroit Michigan 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University Health Sciences  Detroit Michigan USA"},{"name":"Department of Radiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00020840\u2010200404000\u201000013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109610(74)90265\u20107"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0901\u20105027(97)80008\u20102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1054\/ijom.2003.0448"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13010267"},{"issue":"9","key":"e_1_2_10_7_1","first-page":"4092","article-title":"Systemic Therapies for Salivary Gland Adenoid Cystic Carcinoma","volume":"11","author":"Sahara S.","year":"2021","journal-title":"American Journal of Cancer 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