Evidence map›Paper›PMID 34737445›Full record

ArticleNature cell biology2021

FGFR-inhibitor-mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces adaptive therapeutic resistance.

Yihao Li, Xintao Qiu, Xiaoqing Wang, Hui Liu, Renee C Geck, Alok K Tewari, Tengfei Xiao, Alba Font-Tello, Klothilda Lim, Kristen L Jones and 13 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  8. Article
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  12. YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate.International journal of molecular sciences · 2024
    Review
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  14. Review
  15. Super-enhancer RNA mNature genetics · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 3 institutions in 1 country.

Yihao Li *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Xintao Qiu *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8560-7017
Xiaoqing WangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7476-8889
Hui LiuDepartment of Pathology, and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Renee C GeckDepartment of Pathology, and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7812-7675
Alok K TewariDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2617-7499
Tengfei XiaoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alba Font-TelloDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Klothilda LimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Kristen L JonesLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, Boston, MA, USA.
Murry MorrowLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, Boston, MA, USA.
Raga VadhiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Pei-Lun KaoDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Aliya JaberDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Smitha YerrumDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yingtian XieDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Kin-Hoe ChowDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Paloma CejasDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Quang-Dé NguyenLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9043-4413
Henry W LongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
X Shirley LiuCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4736-7339
Alex TokerDepartment of Pathology, and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. myles_brown@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-8213-1658
Harvard University · USDana-Farber Cancer Institute · USBeth Israel Deaconess Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

How cancer cells adapt to evade the therapeutic effects of drugs targeting oncogenic drivers is poorly understood. Here we report an epigenetic mechanism leading to the adaptive resistance of triple-negative breast cancer (TNBC) to fibroblast growth factor receptor (FGFR) inhibitors. Prolonged FGFR inhibition suppresses the function of BRG1-dependent chromatin remodelling, leading to an epigenetic state that derepresses YAP-associated enhancers. These chromatin changes induce the expression of several amino acid transporters, resulting in increased intracellular levels of specific amino acids that reactivate mTORC1. Consistent with this mechanism, addition of mTORC1 or YAP inhibitors to FGFR blockade synergistically attenuated the growth of TNBC patient-derived xenograft models. Collectively, these findings reveal a feedback loop involving an epigenetic state transition and metabolic reprogramming that leads to adaptive therapeutic resistance and provides potential therapeutic strategies to overcome this mechanism of resistance.

Indexed as

Drug Resistance, NeoplasmAmino AcidsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorChromatin Assembly and DisassemblyChromosomal Proteins, Non-HistoneDNA HelicasesDrug SynergismEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMechanistic Target of Rapamycin Complex 1Molecular Targeted TherapyMultiprotein ComplexesAmino AcidsAntineoplastic AgentsChromosomal Proteins, Non-HistoneDNA HelicasesinfigratinibMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNuclear ProteinsPhenylurea CompoundsPyrimidinesReceptors, Fibroblast Growth FactorSMARCA4 protein, humanTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID34737445
OpenAlexW3209822687

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.