{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:56:39Z","timestamp":1781636199541,"version":"3.54.5"},"reference-count":59,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer. Despite recent advances in treating BRAFV600E\u2010driven ATC, therapy resistance remains a significant challenge, often resulting in disease progression and death. Leveraging a focused CRISPR\/KO screen in parallel with a CRISPR\/activation screen, both tailored on response to BRAFV600E inhibitor treatment, we identified TAZ (encoded by WWTR1 gene) deficiency as synthetically lethal with BRAF inhibitor in ATC. TAZ is overexpressed in ATC compared to well\u2010differentiated thyroid tumors. We demonstrate that TAZ\u2010deficient ATC cells display heightened sensitivity to BRAF inhibitors. Using gene essentiality score across cancer cell lines, we found that BRAFV600E\u2010driven cancers are highly sensitive to TAZ loss, unlike their counterparts with wild\u2010type BRAF and non\u2010BRAFV600E. Mechanistically, we demonstrate that dabrafenib triggers the Unfolded Protein Response (UPR) under ER stress and suppresses protein synthesis. TAZ loss represses the UPR, reverses the inhibition of protein synthesis, and triggers increased cell death by ferroptosis in dabrafenib\u2010treated ATC. Collectively, our findings unveil TAZ as a new target to overcome resistance to BRAF inhibitors in undifferentiated thyroid cancer.<\/jats:p>","DOI":"10.1002\/mc.70122","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T18:31:18Z","timestamp":1777228278000},"page":"874-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR\u2010Based Gene Dependency Screens Reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Shawn","family":"Noronha","sequence":"first","affiliation":[{"name":"Surgical Oncology Program, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"},{"name":"Developmental Therapeutics Branch, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology The University of Texas at Austin Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaga","family":"Geneti","sequence":"additional","affiliation":[{"name":"Laboratory Animal Sciences Program, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojian","family":"Li","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[{"name":"NCI Genomics Technology, Laboratory, Cancer Research Technology Program Frederick National Laboratory for Cancer Research\/Frederick  Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sun","sequence":"additional","affiliation":[{"name":"NCI Genomics Technology, Laboratory, Cancer Research Technology Program Frederick National Laboratory for Cancer Research\/Frederick  Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhavi","family":"Gujar","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Furusawa","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, Center for Cancer Research National Cancer Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Lobanov","sequence":"additional","affiliation":[{"name":"Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland USA"},{"name":"Advanced Biomedical Computational Sciences, Frederick National Laboratory for Cancer Research Leidos Biomedical Research, Inc. 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