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Even with surgical and chemotherapeutic interventions, the five-year survival rate is less than 5%. Although combination dabrafenib\/trametinib therapy was recently approved for treatment of the ~25% of ATCs harboring BRAFV600E mutations, there are no approved, effective treatments for BRAF-wildtype disease. Herein, we perform a screen of 1525 drugs and evaluate therapeutic candidates using monolayer cell lines and four corresponding spheroid models of anaplastic thyroid carcinoma. We utilize three-dimensional culture methods, as they have been shown to more accurately recapitulate tumor responses in vivo. These three-dimensional cultures include four distinct ATC spheroid lines representing unique morphology and mutational drivers to provide drug prioritization that will be more readily translatable to the clinic. Using this screen, we identify three exceptionally potent compounds (bortezomib, cabazitaxel, and YM155) that have established safety profiles and could potentially be moved into clinical trial for the treatment of anaplastic thyroid carcinoma, a disease with few treatment options.<\/jats:p>","DOI":"10.3390\/cancers14081855","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T13:39:51Z","timestamp":1649338791000},"page":"1855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Kensey","family":"Bergdorf","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-900X","authenticated-orcid":false,"given":"Joshua A.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Vanderbilt Institute of Chemical Biology-High-Throughput Screening Facility, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Westover","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute of Chemical Biology-High-Throughput Screening Facility, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Phifer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Murphy","sequence":"additional","affiliation":[{"name":"Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-4308","authenticated-orcid":false,"given":"Darren R.","family":"Tyson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-6156","authenticated-orcid":false,"given":"Ethan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-3207","authenticated-orcid":false,"given":"Vivian L.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ref_1","first-page":"5888","article-title":"The incidence and survival analysis for anaplastic thyroid cancer: A SEER database analysis","volume":"11","author":"Lin","year":"2019","journal-title":"Am. 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Sci., 22.","DOI":"10.3390\/ijms22041961"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/8\/1855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:37Z","timestamp":1760136577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/8\/1855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,7]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["cancers14081855"],"URL":"https:\/\/doi.org\/10.3390\/cancers14081855","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,7]]}}}