{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T08:55:59Z","timestamp":1775292959127,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE023227"],"award-info":[{"award-number":["R01DE023227"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Salivary gland adenoid cystic carcinoma (ACC) is a rare and challenging form of head and neck cancer, particularly difficult to treat once it progresses to recurrent or metastatic disease. In this study, we evaluate the cytotoxicity and anti\u2010tumorigenic effects of CWP232291, a first\u2010in\u2010class small molecule inhibitor targeting the Wnt\u2013\u03b2\u2010catenin signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumor microarrays of ACC patients and patient\u2010derived xenografts (PDX) were evaluated by immunohistochemistry, RNA\u2010seq, and qRT\u2010PCR analysis for \u03b2\u2010catenin. The effects of CWP232291 were determined by cytotoxic, qRT\u2010PCR, and immunoblotting analysis. In\u00a0vivo anti\u2010tumorigenic effects of CWP232291 were evaluated using cell line xenograft and PDX models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Immunohistochemistry analysis revealed that high \u03b2\u2010catenin expression correlated with reduced overall survival in ACC patients. Expression of genes involved in the Wnt\u2013\u03b2\u2010catenin pathway was enriched in PDX samples. In\u00a0vitro cytotoxicity and biochemical assays using MDA\u2010ACC\u201001 and UM\u2010HACC\u20102A cell lines revealed that ACC cells were susceptible to CWP232291. Furthermore, CWP232291 treatment attenuated in\u00a0vivo tumor growth in both cell line xenograft and PDX models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Abnormal Wnt\u2013\u03b2\u2010catenin signaling may play an active role in ACC pathogenesis, and its inhibition by CWP232291 may offer therapeutic potential, representing a promising avenue for further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.28249","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T09:14:19Z","timestamp":1752743659000},"page":"3321-3330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Small Molecule Inhibitor of the Wnt\u2013\u03b2\u2010Catenin Pathway,\n                    <scp>CWP232291<\/scp>\n                    , Inhibits Tumor Growth in Preclinical Models of Salivary Gland Adenoid Cystic Carcinoma"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7408-6373","authenticated-orcid":false,"given":"Joseph O.","family":"Humtsoe","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-4247","authenticated-orcid":false,"given":"Bhumsuk","family":"Keam","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"},{"name":"Department of Internal Medicine Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun\u2010Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-9659","authenticated-orcid":false,"given":"Leilani","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Leonard","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Pothukuchi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Honjo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California San Francisco, Helen Diller Family Comprehensive Cancer Center  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"van Zante","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California San Francisco  San Francisco California 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