Evidence map›Paper›PMID 37541244›Full record

ArticleCancer cell2023

Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer.

Fernando J de Miguel, Claudia Gentile, William W Feng, Shannon J Silva, Akshay Sankar, Francisco Exposito, Wesley L Cai, Mary Ann Melnick, Camila Robles-Oteiza, Madeline M Hinkley and 16 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
16.0field-weighted citation impact, top 1% of its field
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

69 citing papers in PubMed, 96 citations in OpenAlex.

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  4. Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 1 country.

Fernando J de MiguelYale Cancer Center, New Haven, CT 06520, USA.
Claudia GentileDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
William W FengDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Shannon J SilvaDepartment of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Akshay SankarDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Francisco ExpositoYale Cancer Center, New Haven, CT 06520, USA.
Wesley L CaiDepartment of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Mary Ann MelnickYale Cancer Center, New Haven, CT 06520, USA.
Camila Robles-OteizaDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Madeline M HinkleyDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jeanelle A TsaiDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Antja-Voy HartleyDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jin WeiDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Laboratory Medicine, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Anna WurtzYale Cancer Center, New Haven, CT 06520, USA.
Fangyong LiYale Center for Analytical Sciences, Yale School of Public Health, Laboratory of Epidemiology and Public Health, 60 College St, New Haven, CT 06510, USA.
Maria I TokiYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
David L RimmYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Robert HomerYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Craig B WilenDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Laboratory Medicine, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Andrew Z XiaoDepartment of Genetics, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Qin YanYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Don X NguyenYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Pasi A JänneDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: cigall_kadoch@dfci.harvard.edu.
Katerina A PolitiYale Cancer Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, Yale University, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, Yale University, New Haven, CT 06510, USA. Electronic address: katerina.politi@yale.edu.
Yale Cancer Center · USYale University · USDana-Farber Cancer Institute · USHarvard University · USBroad Institute · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1M
Development of Combination Therapies to Delay/Prevent Acquired Drug ResistanceR35CA220497 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2018 to 2024
$7.2M
Uncovering the Biology of Resistance to Tyrosine Kinase Inhibitors in EGFR Mutant Lung Cancer Patient-Derived Models.U01CA235747 · NCI · YALE UNIVERSITY · PI NGUYEN, DON X, POLITI, KATERINA ABIGAIL · 2019 to 2023
$3.9M
Yale Cancer Biology Training GrantT32CA193200 · NCI · YALE UNIVERSITY · PI PETER M GLAZER, Qin Yan · 2016 to 2026
$3.6M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA016359NCI NIH HHS P50 CA196530NCI NIH HHS R35 CA220497NCI NIH HHS T32 CA193200NCI NIH HHS U01 CA235747
6 · The paper itself

Abstract

Acquired resistance to tyrosine kinase inhibitors (TKI), such as osimertinib used to treat EGFR-mutant lung adenocarcinomas, limits long-term efficacy and is frequently caused by non-genetic mechanisms. Here, we define the chromatin accessibility and gene regulatory signatures of osimertinib sensitive and resistant EGFR-mutant cell and patient-derived models and uncover a role for mammalian SWI/SNF chromatin remodeling complexes in TKI resistance. By profiling mSWI/SNF genome-wide localization, we identify both shared and cancer cell line-specific gene targets underlying the resistant state. Importantly, genetic and pharmacologic disruption of the SMARCA4/SMARCA2 mSWI/SNF ATPases re-sensitizes a subset of resistant models to osimertinib via inhibition of mSWI/SNF-mediated regulation of cellular programs governing cell proliferation, epithelial-to-mesenchymal transition, epithelial cell differentiation, and NRF2 signaling. These data highlight the role of mSWI/SNF complexes in supporting TKI resistance and suggest potential utility of mSWI/SNF inhibitors in TKI-resistant lung cancers.

Indexed as

Lung NeoplasmsTyrosine Kinase InhibitorsAcrylamidesAniline CompoundsAnimalsChromatinChromatin Assembly and DisassemblyDNA HelicasesErbB ReceptorsHumansIndolesMammalsMutationNuclear ProteinsProtein Kinase InhibitorsPyrimidinesAcrylamidesAniline CompoundsChromatinDNA HelicasesEGFR protein, humanErbB ReceptorsIndolesNuclear ProteinsosimertinibProtein Kinase InhibitorsPyrimidinesSMARCA4 protein, humanTranscription FactorsTyrosine Kinase Inhibitors

Identifiers

PMID37541244
PMCPMC10957226
OpenAlexW4385546051

What OpenQuestion holds

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Registered trials

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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.