{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:19:34Z","timestamp":1791983974560,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB\u2013NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.<\/jats:p>","DOI":"10.3390\/cancers14040992","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["A Contemporary Review of Molecular Therapeutic Targets for Adenoid Cystic Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Lauren E.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivienne","family":"Au","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara E.","family":"Mokhtari","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Goss","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-7762","authenticated-orcid":false,"given":"Daniel L.","family":"Faden","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Varvares","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1001\/archotol.129.11.1193","article-title":"Clinicopathologic Predictors and Impact of Distant Metastasis From Adenoid Cystic Carcinoma of the Head and Neck","volume":"129","author":"Sung","year":"2003","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/1097-0142(19860201)57:3<519::AID-CNCR2820570319>3.0.CO;2-V","article-title":"Adenoid cystic salivary gland carcinoma: A histopathologic review of treatment failure patterns","volume":"57","author":"Matsuba","year":"1986","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0002-9610(97)00153-0","article-title":"Distant metastasis in adenoid cystic carcinoma of salivary origin","volume":"174","author":"Spiro","year":"1997","journal-title":"Am. J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.oraloncology.2016.12.016","article-title":"Systemic therapy in metastatic salivary gland carcinomas: A pathology-driven paradigm?","volume":"66","author":"Alfieri","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_5","first-page":"3045","article-title":"Clinical outcomes and prognostic factors of adenoid cystic carcinoma of the head and neck","volume":"37","author":"Jang","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1046\/j.1365-2273.1997.00041.x","article-title":"Adenoid cystic carcinoma of the head and neck","volume":"22","author":"Jones","year":"1997","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e5964","DOI":"10.1097\/MD.0000000000005964","article-title":"Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china","volume":"96","author":"Ouyang","year":"2017","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S1470-2045(10)70245-X","article-title":"Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: A systematic review","volume":"12","author":"Laurie","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"174","DOI":"10.5195\/jmla.2021.962","article-title":"PRISMA-S Group PRISMA-S: An extension to the PRISMA statement for reporting literature searches in systematic reviews","volume":"109","author":"Rethlefsen","year":"2021","journal-title":"J. Med. Libr. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/ng.2643","article-title":"The mutational landscape of adenoid cystic carcinoma","volume":"45","author":"Ho","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1126\/science.1208130","article-title":"The Mutational Landscape of Head and Neck Squamous Cell Carcinoma","volume":"333","author":"Stransky","year":"2011","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1158\/1940-6207.CAPR-15-0316","article-title":"Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma","volume":"9","author":"Rettig","year":"2016","journal-title":"Cancer Prev. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1172\/JCI128227","article-title":"Genetic hallmarks of recurrent\/metastatic adenoid cystic carcinoma","volume":"129","author":"Ho","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.oraloncology.2005.12.026","article-title":"A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands","volume":"43","author":"Pfeffer","year":"2007","journal-title":"Oral Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1200\/JCO.2005.06.125","article-title":"Imatinib Mesylate in Patients with Adenoid Cystic Cancers of the Salivary Glands Expressing c-kit: A Princess Margaret Hospital Phase II Consortium Study","volume":"23","author":"Hotte","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.bjoms.2010.09.013","article-title":"Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma","volume":"49","author":"Ghosal","year":"2011","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/annonc\/mdv537","article-title":"Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors","volume":"27","author":"Wong","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1093\/annonc\/mdr522","article-title":"A phase II study of sunitinib in recurrent and\/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: Current progress and challenges in evaluating molecularly targeted agents in ACC","volume":"23","author":"Chau","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.oraloncology.2008.07.010","article-title":"Cetuximab in recurrent and\/or metastatic salivary gland carcinomas: A phase II study","volume":"45","author":"Locati","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3978","DOI":"10.1200\/JCO.2007.11.8612","article-title":"Phase II Study of Lapatinib in Recurrent or Metastatic Epidermal Growth Factor Receptor and\/or erbB2 Expressing Adenoid Cystic Carcinoma and Non\u2013Adenoid Cystic Carcinoma Malignant Tumors of the Salivary Glands","volume":"25","author":"Agulnik","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.1158\/1078-0432.CCR-16-2942","article-title":"A Phase II Study of Dovitinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma","volume":"23","author":"Dillon","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1002\/cncr.32754","article-title":"Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: Activity and quality of life","volume":"126","author":"Locati","year":"2020","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1200\/JCO.18.01859","article-title":"Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma","volume":"37","author":"Tchekmedyian","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1200\/JCO.2016.34.15_suppl.6086","article-title":"PACSA: Phase II study of pazopanib in patients with progressive recurrent or metastatic (R\/M) salivary gland carcinoma (SGC)","volume":"34","author":"Guigay","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1093\/annonc\/mdy171","article-title":"A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors","volume":"29","author":"Ferrarotto","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1200\/JCO.2019.37.15_suppl.6083","article-title":"NISCAHN: A phase II, multicenter nonrandomized trial aiming at evaluating nivolumab (N) in two cohorts of patients (pts) with recurrent\/metastatic (R\/M) salivary gland carcinoma of the head and neck (SGCHN), on behalf of the Unicancer Head & Neck Group","volume":"37","author":"Fayette","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ijrobp.2020.08.018","article-title":"A Randomized Phase 2 Study of Pembrolizumab with or Without Radiation in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma","volume":"109","author":"Mahmood","year":"2020","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"v159","DOI":"10.1093\/annonc\/mdz244","article-title":"METEOR-1: A phase I study of GSK3326595, a first-in-class protein arginine methyltransferase 5 (PRMT5) inhibitor, in advanced solid tumours","volume":"30","author":"Siu","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105366","DOI":"10.1016\/j.oraloncology.2021.105366","article-title":"A phase II trial of all-trans retinoic acid (ATRA) in advanced adenoid cystic carcinoma","volume":"119","author":"Hanna","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrc2439","article-title":"MYB function in normal and cancer cells","volume":"8","author":"Ramsay","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/CCO.0000000000000280","article-title":"MYB-fusions and other potential actionable targets in adenoid cystic carcinoma","volume":"28","author":"Ferrarotto","year":"2016","journal-title":"Curr. Opin Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ng.3502","article-title":"An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma","volume":"48","author":"Drier","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104690","DOI":"10.1016\/j.oraloncology.2020.104690","article-title":"Long-term outcomes and clinicogenomic correlates in recurrent, metastatic adenoid cystic carcinoma","volume":"106","author":"Hanna","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1200\/JCO.2018.36.15_suppl.6053","article-title":"Comprehensive proteomic and genomic profiling to identify therapeutic targets in adenoid cystic carcinoma","volume":"36","author":"Thyparambil","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_35","first-page":"778","article-title":"Abstract 778: Potential drug targets for adenoid cystic carcinoma elucidated by proteogenomic analysis","volume":"78","author":"Thyparambil","year":"2018","journal-title":"Experimental and Molecular Therapeutics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.anai.2021.03.003","article-title":"Our current understanding of checkpoint inhibitor therapy in cancer immunotherapy","volume":"126","author":"Goleva","year":"2021","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41389-020-0194-3","article-title":"ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma","volume":"9","author":"Andersson","year":"2020","journal-title":"Oncogenesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17043","DOI":"10.18632\/oncotarget.24818","article-title":"Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma","volume":"9","author":"Saida","year":"2018","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1158\/2159-8290.CD-15-0859","article-title":"Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma","volume":"6","author":"Brayer","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yusenko, M.V., Biyanee, A., Frank, D., K\u00f6hler, L.H.F., Andersson, M.K., Khandanpour, C., Schobert, R., Stenman, G., Biersack, B., and Klempnauer, K.-H. (2021). Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. Cancers, 14.","DOI":"10.3390\/cancers14010043"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2021.07.010","article-title":"Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner","volume":"520","author":"Yusenko","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"djx017","DOI":"10.1093\/jnci\/djx017","article-title":"Targeting the Oncogenic Transcriptional Regulator MYB in Adenoid Cystic Carcinoma by Inhibition of IGF1R\/AKT Signaling","volume":"109","author":"Andersson","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.2147\/DDDT.S89114","article-title":"Receptor tyrosine kinase (c-Kit) inhibitors: A potential therapeutic target in cancer cells","volume":"10","author":"Babaei","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_44","first-page":"956","article-title":"Kit protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma","volume":"12","author":"Holst","year":"1999","journal-title":"Mod. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1093\/annonc\/mdt338","article-title":"Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours","volume":"24","author":"Cros","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/modpathol.2009.95","article-title":"Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland","volume":"22","author":"Vila","year":"2009","journal-title":"Mod. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.oraloncology.2005.05.005","article-title":"Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland","volume":"41","author":"Freier","year":"2005","journal-title":"Oral Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.oraloncology.2009.01.013","article-title":"KRAS status and epidermal growth factor receptor expression as determinants for anti-EGFR therapies in salivary gland carcinomas","volume":"45","author":"Dahse","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/hed.23647","article-title":"Phase II study of gefitinib in patients with advanced salivary gland cancers","volume":"37","author":"Jakob","year":"2014","journal-title":"Head Neck"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"vi335","DOI":"10.1093\/annonc\/mdw376.24","article-title":"Dovitinib in advanced adenoid cystic carcinoma of the salivary glands: Ontario Clinical Oncology Group DOVE trial","volume":"27","author":"Hotte","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/hed.25468","article-title":"Salivary gland tumors: Molecular characterization and therapeutic advances for metastatic disease","volume":"41","author":"Schvartsman","year":"2019","journal-title":"Head Neck"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.hoc.2021.05.011","article-title":"Salivary Gland Cancers","volume":"35","author":"Tchekmedyian","year":"2021","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"873","DOI":"10.6004\/jnccn.2020.0031","article-title":"Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology","volume":"18","author":"Pfister","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_54","unstructured":"Memorial Sloan Kettering Cancer Center (2021, December 20). Lenvatinib and Pembrolizumab in People with Advanced Adenoid Cystic Carcinoma and Other Salivary Gland Cancers, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04209660."},{"key":"ref_55","first-page":"212","article-title":"Clinico-pathological significance of microvessel density and vascular endothelial growth factor expression in adenoid cystic carcinoma of salivary glands","volume":"36","author":"Li","year":"2001","journal-title":"Zhonghua Kou Qiang Yi Xue Za Zhi"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4143\/crt.2015.093","article-title":"VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma","volume":"48","author":"Park","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1034\/j.1600-0714.2003.00145.x","article-title":"Immunohistochemical and genetic analysis of mandibular cysts in heterozygous ptc knockout mice","volume":"32","author":"Kimi","year":"2003","journal-title":"J. Oral Pathol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Misiorek, J.O., Przybyszewska-Podstawka, A., Ka\u0142afut, J., Paziewska, B., Rolle, K., Rivero-M\u00fcller, A., and Nees, M. (2021). Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis. Cells, 10.","DOI":"10.3390\/cells10010094"},{"key":"ref_59","first-page":"456","article-title":"Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck","volume":"39","author":"Reinhard","year":"2016","journal-title":"Head Neck"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1200\/JCO.2016.67.5264","article-title":"Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors","volume":"35","author":"Ferrarotto","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e17053","DOI":"10.1200\/jco.2015.33.15_suppl.e17053","article-title":"Genomic testing may offer therapeutic opportunity in salivary gland cancers","volume":"33","author":"Chintakuntlawar","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6885","DOI":"10.18632\/oncotarget.2321","article-title":"NOTCH1 signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma","volume":"5","author":"Su","year":"2014","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"81725","DOI":"10.18632\/oncotarget.20879","article-title":"Taking it up a NOTCH: A novel subgroup of ACC is identified","volume":"8","author":"Ferrarotto","year":"2017","journal-title":"Oncotarget"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"580141","DOI":"10.3389\/fonc.2020.580141","article-title":"Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease","volume":"10","author":"Souza","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1200\/JCO.2021.39.15_suppl.3020","article-title":"Phase 1 study of CB-103, a novel first-in-class inhibitor of the CSL-NICD gene transcription factor complex in human cancers","volume":"39","author":"Miranda","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_66","unstructured":"Ayala Pharmaceuticals, I. (2021, December 21). A Study of AL101 in Patients with Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations (ACCURACY), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03691207."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1677\/joe.0.1800055","article-title":"Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands","volume":"180","author":"Valimaa","year":"2004","journal-title":"J. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2559.2011.04095.x","article-title":"Oestrogen receptor \u03b2 in adenoid cystic carcinoma of salivary glands","volume":"60","author":"Marques","year":"2012","journal-title":"Histopathology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/leu.2011.46","article-title":"Targeting the translational apparatus to improve leukemia therapy: Roles of the PI3K\/PTEN\/Akt\/mTOR pathway","volume":"25","author":"Martelli","year":"2011","journal-title":"Leukemia"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kim, D.-W., Oh, D.-Y., Shin, S.H., Kang, J.H., Cho, B.C., Chung, J.-S., Kim, H., Park, K.U., Kwon, J.H., and Han, J.-Y. (2014). A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-795"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s41416-020-0988-2","article-title":"Phase 1 safety and pharmacodynamic study of lenalidomide combined with everolimus in patients with advanced solid malignancies with efficacy signal in adenoid cystic carcinoma","volume":"123","author":"Harvey","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11477","DOI":"10.18632\/oncotarget.3411","article-title":"High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy","volume":"6","author":"Liu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_73","first-page":"764","article-title":"Inhibition of mTOR reduce Stat3 and PAI related angiogenesis in salivary gland adenoid cystic carcinoma","volume":"4","author":"Yu","year":"2014","journal-title":"Am. J. Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/cam4.1293","article-title":"AKT3 drives adenoid cystic carcinoma development in salivary glands","volume":"7","author":"Zboray","year":"2017","journal-title":"Cancer Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/gb4184","article-title":"Cyclin-dependent kinases","volume":"15","author":"Malumbres","year":"2014","journal-title":"Genome Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1200\/JCO.2019.37.15_suppl.6084","article-title":"A phase II trial cohort of nivolumab plus ipilimumab in patients (Pts) with recurrent\/metastatic adenoid cystic carcinoma (R\/M ACC)","volume":"37","author":"Tchekmedyian","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00106-019-00760-9","article-title":"Maligne Speicheldr\u00fcsentumoren\u2014Highlights der ASCO-Jahrestagung 2019","volume":"67","author":"Doescher","year":"2019","journal-title":"HNO"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1158\/2326-6066.CIR-16-0031","article-title":"Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes","volume":"4","author":"Sridharan","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.oraloncology.2018.11.028","article-title":"Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands","volume":"88","author":"Mosconi","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_80","first-page":"1138","article-title":"Abstract 1138: PRMT5 inhibition downregulates MYB and NOTCH1 signaling, key molecular drivers of adenoid cystic carcinoma","volume":"81","author":"Carter","year":"2021","journal-title":"Exp. Mol. Ther."},{"key":"ref_81","unstructured":"Radboud University (2021, December 20). Lutetium-177-PSMA Radioligand Therapy in Advanced Salivary Gland Cancer Patients (LUPSA), Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04291300."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1038\/labinvest.2011.105","article-title":"Development and characterization of xenograft model systems for adenoid cystic carcinoma","volume":"91","author":"Moskaluk","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_83","first-page":"773","article-title":"Establishment of patient-derived xenograft models of adenoid cystic carcinoma to assess pre-clinical efficacy of combination therapy of a PI3K inhibitor and retinoic acid","volume":"11","author":"Sun","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"11410","DOI":"10.1038\/s41598-017-11764-2","article-title":"A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.oraloncology.2011.01.009","article-title":"Adenoid cystic carcinoma: A rare clinical entity and literature review","volume":"47","author":"Gondivkar","year":"2011","journal-title":"Oral Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/COC.0b013e3181d26d45","article-title":"Determinants and patterns of survival in adenoid cystic carcinoma of the head and neck, including an analysis of adjuvant radiation therapy","volume":"34","author":"Lloyd","year":"2011","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/hed.10400","article-title":"Salivary gland carcinoma: Independent prognostic factors for locoregional control, distant metastases, and overall survival: Results of the Dutch head and neck oncology cooperative group","volume":"26","author":"Terhaard","year":"2004","journal-title":"Head Neck"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"18740","DOI":"10.1073\/pnas.0909114106","article-title":"Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck","volume":"106","author":"Persson","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1158\/1078-0432.CCR-10-0463","article-title":"Comprehensive Analysis of the MYB-NFIB Gene Fusion in Salivary Adenoid Cystic Carcinoma: Incidence, Variability, and Clinicopathologic Significance","volume":"16","author":"Mitani","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1158\/1078-0432.CCR-20-1192","article-title":"Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets","volume":"27","author":"Ferrarotto","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/cyt.12789","article-title":"Fine-needle aspiration cytology of extra-salivary adenoid cystic carcinoma","volume":"31","author":"Kapatia","year":"2019","journal-title":"Cytopathology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:20:40Z","timestamp":1760134840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":91,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14040992"],"URL":"https:\/\/doi.org\/10.3390\/cancers14040992","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]}}}