Evidence map›Paper›PMID 42035477›Full record

ArticleMolecular carcinogenesis2026

CRISPR-Based Gene Dependency Screens Reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer.

Shawn Noronha, Yue Liu, Gaga Geneti, Haojian Li, Xiaolin Wu, David Sun, Vaibhavi Gujar, Takashi Furusawa, Alexei Lobanov, Maggie Cam and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular carcinogenesis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Shawn NoronhaSurgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Yue LiuInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA.
Gaga GenetiLaboratory Animal Sciences Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Haojian LiDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Xiaolin WuNCI Genomics Technology, Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research/Frederick, Maryland, USA.
David SunNCI Genomics Technology, Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research/Frederick, Maryland, USA.
Vaibhavi GujarDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Takashi FurusawaDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Alexei LobanovCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Maggie CamCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-8190-9766
Lipika R PalCancer Data Science Lab/Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland, USA.
Nishanth U NairCancer Data Science Lab/Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland, USA.
Chi-Ping DayCancer Data Science Lab/Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland, USA.
Eytan RuppinCancer Data Science Lab/Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland, USA.
Chandrayee GhoshDepartment of Surgery and Stanford Cancer Institute, Stanford University, Stanford, California, USA.
Jiangnan HuDepartment of Surgery and Stanford Cancer Institute, Stanford University, Stanford, California, USA.
Bhavishya RamamoorthySurgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Suresh KumarDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Thorkell AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
King ChanProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Maura O'NeillProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Raj ChariGenome Modification Core, Laboratory Animal Sciences Program, Frederick National Lab for Cancer Research, Frederick, Maryland, USA.
Yves PommierDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Jaydira Del RiveroDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.ORCID 0000-0001-9710-4030
Urbain WeyemiDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Electron KebebewDepartment of Surgery and Stanford Cancer Institute, Stanford University, Stanford, California, USA.
Myriem BoufraqechSurgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.ORCID 0000-0001-7700-9992

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer. Despite recent advances in treating BRAFV600E-driven 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-differentiated thyroid tumors. We demonstrate that TAZ-deficient ATC cells display heightened sensitivity to BRAF inhibitors. Using gene essentiality score across cancer cell lines, we found that BRAFV600E-driven cancers are highly sensitive to TAZ loss, unlike their counterparts with wild-type BRAF and non-BRAFV600E. 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-treated ATC. Collectively, our findings unveil TAZ as a new target to overcome resistance to BRAF inhibitors in undifferentiated thyroid cancer.

Indexed as

Drug Resistance, NeoplasmProtein Kinase InhibitorsProto-Oncogene Proteins B-rafThyroid Carcinoma, AnaplasticThyroid NeoplasmsCell Line, TumorCRISPR-Cas SystemsGene Expression Regulation, NeoplasticHumansImidazolesOximesTranscriptional Coactivator with PDZ-Binding Motif ProteinsUnfolded Protein ResponseBRAF protein, humandabrafenibImidazolesOximesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafTranscriptional Coactivator with PDZ-Binding Motif ProteinsWWTR1 protein, human

Identifiers

PMID42035477
PMCPMC13271530

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.