{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:40:59Z","timestamp":1785426059524,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea University Ansan Hospital","award":["O2414021"],"award-info":[{"award-number":["O2414021"]}]},{"award":["O2414021"],"award-info":[{"award-number":["O2414021"]}],"id":[{"id":"https:\/\/ror.org\/05yp5js06","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive malignancy characterized by rapid progression, early metastasis, and extremely poor survival outcomes. Effective therapeutic options remain limited, highlighting the need for efficient and biologically relevant preclinical drug-discovery platforms. In this study, high-throughput compound screening using human ATC cell lines identified ANC-3 as a potential anticancer candidate. Its antitumor activity was evaluated through cytotoxicity and functional assays, zebrafish xenograft validation with live fluorescence imaging, colony-formation assays, and bulk RNA sequencing with pathway enrichment analyses. ANC-3 demonstrated consistent antitumor effects by significantly inhibiting cell viability, migration, invasion, and clonogenic survival, while also suppressing tumor growth in zebrafish xenograft models. Transcriptomic analyses revealed modulation of multiple oncogenic pathways, including MAPK, Ras, and NF-\u03baB signaling. Collectively, these findings support zebrafish xenograft-based screening as a rapid and scalable platform for ATC drug discovery and suggest ANC-3 as a promising multi-pathway inhibitor warranting further preclinical development.<\/jats:p>","DOI":"10.3390\/ijms27125222","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:33:44Z","timestamp":1781073224000},"page":"5222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of ANC-3 as a Novel Therapeutic Candidate for Anaplastic Thyroid Cancer Through Drug Screening and Multi-Platform Validation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4667-3986","authenticated-orcid":false,"given":"Dorjsuren","family":"Tsagaankhuu","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"},{"name":"Biomedical Research Center, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9051-9313","authenticated-orcid":false,"given":"Hyunwoo","family":"Baek","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"},{"name":"Division of Oncology and Hematology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungyoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Oncology and Hematology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1501-390X","authenticated-orcid":false,"given":"Soonyoung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"},{"name":"Biomedical Research Center, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/ajco.14106","article-title":"Anaplastic thyroid cancer: A review of recent evidence and summary of an Australian institutional protocol","volume":"20","author":"Lawless","year":"2024","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Guo, H., Zhang, J., Jia, Y., Liu, Z., Qi, Y., Sun, C., Cai, Z., and Wu, J. (2025). Trends in incidence, mortality, and conditional survival of anaplastic thyroid cancer over the last two decades in the USA. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1585679"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101788","DOI":"10.1016\/j.ando.2025.101788","article-title":"ENDOCAN TUTHYREF network consensus recommendations: Anaplastic thyroid cancer","volume":"86","author":"Lamartina","year":"2025","journal-title":"Ann. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1089\/thy.2020.0944","article-title":"2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer: American Thyroid Association Anaplastic Thyroid Cancer Guidelines Task Force","volume":"31","author":"Bible","year":"2021","journal-title":"Thyroid"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nrendo.2017.76","article-title":"Anaplastic thyroid carcinoma: From clinicopathology to genetics and advanced therapies","volume":"13","author":"Molinaro","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1172\/JCI85271","article-title":"Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers","volume":"126","author":"Landa","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1158\/1078-0432.CCR-18-0373","article-title":"Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers","volume":"24","author":"Pozdeyev","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1016\/j.surge.2023.10.002","article-title":"Anaplastic thyroid cancer:Improved understanding of what remains a deadly disease","volume":"22","author":"Cleere","year":"2024","journal-title":"Surgeon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1200\/JCO.19.02727","article-title":"PD-1 Blockade in Anaplastic Thyroid Carcinoma","volume":"38","author":"Capdevila","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21053\/ceo.2024.00164","article-title":"Exploring the Role of the KCNK1 Potassium Channel and Its Inhibition Using Quinidine in Treating Head and Neck Squamous Cell Carcinoma","volume":"17","author":"Baek","year":"2024","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/JCO.2017.73.6785","article-title":"Dabrafenib and Trametinib Treatment in Patients with Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer","volume":"36","author":"Subbiah","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1089\/thy.2012.0302","article-title":"American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer","volume":"22","author":"Smallridge","year":"2012","journal-title":"Thyroid"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1158\/2159-8290.CD-14-0001","article-title":"Patient-derived xenograft models: An emerging platform for translational cancer research","volume":"4","author":"Hidalgo","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrclinonc.2012.61","article-title":"Patient-derived tumour xenografts as models for oncology drug development","volume":"9","author":"Tentler","year":"2012","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E8234","DOI":"10.1073\/pnas.1618389114","article-title":"Single-cell functional and chemosensitive profiling of combinatorial colorectal therapy in zebrafish xenografts","volume":"114","author":"Fior","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.stem.2007.11.002","article-title":"Transparent adult zebrafish as a tool for in vivo transplantation analysis","volume":"2","author":"White","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/nprot.2010.150","article-title":"Hypoxia-induced metastasis model in embryonic zebrafish","volume":"5","author":"Rouhi","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"a037077","DOI":"10.1101\/cshperspect.a037077","article-title":"Zebrafish In Vivo Models of Cancer and Metastasis","volume":"10","author":"Astell","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1021\/acs.jmedchem.2c00135","article-title":"Discovery of 4-Hydroxyquinazoline Derivatives as Small Molecular BET\/PARP1 Inhibitors That Induce Defective Homologous Recombination and Lead to Synthetic Lethality for Triple-Negative Breast Cancer Therapy","volume":"65","author":"Zhang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/hc.21057","article-title":"Synthesis of novel amide derivatives with in vitro antiproliferative and cytotoxic activity","volume":"24","author":"Liu","year":"2013","journal-title":"Heteroat. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jconrel.2013.04.023","article-title":"Infusion of imaging and therapeutic molecules into the plant virus-based carrier cowpea mosaic virus: Cargo-loading and delivery","volume":"172","author":"Yildiz","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_22","first-page":"R173","article-title":"Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers","volume":"29","author":"Hofmann","year":"2022","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1089\/thy.2022.0704","article-title":"Challenges and Strategies to Combat Resistance Mechanisms in Thyroid Cancer Therapeutics","volume":"33","author":"Gild","year":"2023","journal-title":"Thyroid"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.annonc.2021.12.014","article-title":"Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: Updated analysis from the phase II ROAR basket study","volume":"33","author":"Subbiah","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_25","first-page":"334","article-title":"Immunotherapy in Anaplastic Thyroid Cancer: Much Yet to Be Learned","volume":"7","author":"Bible","year":"2021","journal-title":"AACE Clin. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1089\/thy.2022.0073","article-title":"An Evaluation of Clinical Efficacy of Immune Checkpoint Inhibitors for Patients with Anaplastic Thyroid Carcinoma","volume":"32","author":"Hatashima","year":"2022","journal-title":"Thyroid"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3803\/EnM.2022.1636","article-title":"Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models","volume":"37","author":"Jeon","year":"2022","journal-title":"Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:38:03Z","timestamp":1781073483000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125222"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125222","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}