{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:35:20Z","timestamp":1791408920073,"version":"4.3.3"},"reference-count":80,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New York State Department of Health\/Empire Clinical Research Investigator Program","award":["30121-101"],"award-info":[{"award-number":["30121-101"]}]},{"award":["30121-101"],"award-info":[{"award-number":["30121-101"]}],"id":[{"id":"https:\/\/ror.org\/04hf5kq57","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive follicular cell-derived malignancy characterized by rapid progression, profound dedifferentiation, and marked resistance to conventional therapy. Despite frequent involvement of major oncogenic pathways, ATC does not exhibit a universal driver mutation, suggesting that its pathogenesis reflects convergence upon shared biological hallmarks rather than dependence on a single molecular event. This review describes the principal mechanistic programs that define the ATC phenotype: disruption of cell-cycle and apoptotic control through alterations in TP53, CDKN2A\/B, and aberrant MAPK activation; metabolic adaptations involving glycolysis, glutaminolysis, and mitochondrial one-carbon metabolism; reprogramming of canonical stress response pathways including ER stress and hypoxia signaling; and dynamic remodeling of the tumor microenvironment through cytokine-driven paracrine networks and immune modulation. Collectively, these processes cooperate to generate a highly proliferative, stress-tolerant, immune-inflamed yet immunosuppressed tumor state. A mechanistic understanding of these convergent pathways is essential for rational therapeutic development and for overcoming the profound clinical resistance that defines ATC.<\/jats:p>","DOI":"10.3390\/ijms27167156","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:10:24Z","timestamp":1786374624000},"page":"7156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Convergent Mechanistic Pathways Driving the Anaplastic Phenotype in Thyroid Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7630-5001","authenticated-orcid":false,"given":"Anthony","family":"Centone","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"DeSouza","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of R&D, General Nutraceutical Technology, LLC., Briarcliff Manor, NY 10510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Moscatello","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-1535","authenticated-orcid":false,"given":"David","family":"Garber","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hemmerdinger","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine M.","family":"Rotsides","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj K.","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-7960","authenticated-orcid":false,"given":"Jan","family":"Geliebter","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","unstructured":"Allen, E., and Fingeret, A. 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