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Tumors of the salivary gland exhibit heterogeneous histologic and genetic features and they are subdivided into different subtypes, with adenoid cystic carcinomas (<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>) being one of the most abundant. Treatment of <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> patients is afflicted by high recurrence rates, the high potential of the tumors to metastasize, as well as the poor response of <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> to chemotherapy. A prerequisite for the development of targeted therapies is insightful genetic information for driver core cancer pathways. Here, we developed a transgenic mouse model toward establishment of a preclinical model. There is currently no available mouse model for adenoid cystic carcinomas as a rare disease entity to serve as a test system to block salivary gland tumors with targeted therapy. Based on tumor genomic data of <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> patients, a key role for the activation of the <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\u2010<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> pathway was suggested in tumors of secretory glands. Therefore, we investigated the role of <jats:italic>Akt3<\/jats:italic> expression in tumorigenesis and report that <jats:italic>Akt3<\/jats:italic> overexpression results in <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> of salivary glands with 100% penetrance, while abrogation of transgenic <jats:italic>Akt3<\/jats:italic> expression could revert the phenotype. In summary, our findings validate a novel mouse model to study <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> and highlight the druggable potential of <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>3 in the treatment of salivary gland patients.<\/jats:p>","DOI":"10.1002\/cam4.1293","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T06:08:54Z","timestamp":1514441334000},"page":"445-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>AKT<\/scp>3 drives adenoid cystic carcinoma development in salivary glands"],"prefix":"10.1002","volume":"7","author":[{"given":"Katalin","family":"Zboray","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Cancer Research (LBI\u2010CR)  Vienna 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