Evidence map›Paper›PMID 32442403›Full record

ArticleCancer cell2020

SETD5-Coordinated Chromatin Reprogramming Regulates Adaptive Resistance to Targeted Pancreatic Cancer Therapy.

Zhentian Wang, Simone Hausmann, Ruitu Lyu, Tie-Mei Li, Shane M Lofgren, Natasha M Flores, Mary E Fuentes, Marcello Caporicci, Ze Yang, Matthew Joseph Meiners and 12 more

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

Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 106 citations in OpenAlex.

  1. Article
  2. Review
  3. Integrative Analysis UncoversCurrent issues in molecular biology · 2026
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  6. Article
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  8. Article
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  16. Article
  17. Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Review
  18. Transcriptional repression by HDAC3 mediates T cell exclusion fromProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Article
  20. Review

1 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

22 authors at 6 institutions in 1 country.

Zhentian WangDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Simone HausmannDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ruitu LyuDepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Tie-Mei LiDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Shane M LofgrenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Natasha M FloresDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mary E FuentesDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Marcello CaporicciDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ze YangDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Matthew Joseph MeinersEpiCypher Inc., Durham, NC 27709, USA.
Marcus Adrian CheekEpiCypher Inc., Durham, NC 27709, USA.
Sarah Ann HowardEpiCypher Inc., Durham, NC 27709, USA.
Lichao ZhangChan Zuckenberg Biohub, Stanford, CA 94305, USA.
Joshua Eric EliasChan Zuckenberg Biohub, Stanford, CA 94305, USA.
Michael P KimDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anirban MaitraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Huamin WangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Michael Cory BassikDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael-Christopher KeoghEpiCypher Inc., Durham, NC 27709, USA.
Julien SageDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Or GozaniDepartment of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: ogozani@stanford.edu.
Pawel K MazurDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: pkmazur@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USStanford University · USEpiCypher (United States) · USChan Zuckerberg Initiative (United States) · USStanford Medicine · USUniversity of Chicago · US

Funding

Accelerating drug development and repurposing using systematic genetic interactioDP2HD084069 · NICHD · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C · 2014 to 2014
$2.4M
Role of SETD5 in Chromatin Regulation and TumorigenesisR01CA236949 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAZUR, PAWEL K. · 2019 to 2023
$1.9M
Barcoded nucleosomes for analyzing combinatorial epigenetic regulatorsR44GM116584 · NIGMS · EPICYPHER, INC. · PI SUN, ZU-WEN · 2017 to 2018
$1.6M
Mechanisms of translational output control in pancreatic cancerK99CA255936 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAUSMANN, SIMONE CHRISTINE · 2021 to 2022
$224k
NCI NIH HHS K99 CA255936NCI NIH HHS R01 CA236949NICHD NIH HHS DP2 HD084069NIGMS NIH HHS R44 GM116584
6 · The paper itself

Abstract

Molecular mechanisms underlying adaptive targeted therapy resistance in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Here, we identify SETD5 as a major driver of PDAC resistance to MEK1/2 inhibition (MEKi). SETD5 is induced by MEKi resistance and its deletion restores refractory PDAC vulnerability to MEKi therapy in mouse models and patient-derived xenografts. SETD5 lacks histone methyltransferase activity but scaffolds a co-repressor complex, including HDAC3 and G9a. Gene silencing by the SETD5 complex regulates known drug resistance pathways to reprogram cellular responses to MEKi. Pharmacological co-targeting of MEK1/2, HDAC3, and G9a sustains PDAC tumor growth inhibition in vivo. Our work uncovers SETD5 as a key mediator of acquired MEKi therapy resistance in PDAC and suggests a context for advancing MEKi use in the clinic.

Indexed as

Drug Resistance, NeoplasmMolecular Targeted TherapyAnimalsApoptosisCarcinoma, Pancreatic DuctalCell ProliferationChromatinFemaleHistocompatibility AntigensHistone Deacetylase 3Histone DeacetylasesHistone-Lysine N-MethyltransferaseHumansMAP Kinase Kinase 1MAP Kinase Kinase 2MethyltransferasesChromatinEHMT2 protein, humanHistocompatibility AntigensHistone Deacetylase 3Histone DeacetylasesHistone-Lysine N-MethyltransferaseMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2MethyltransferasesProtein Kinase InhibitorsPyridonesPyrimidinonesSETD5 protein, humanSmall Molecule LibrariestrametinibKRASlysine methylationMEK inhibitionpancreatic cancerprotein methylationRAS signalingSETD5

Identifiers

PMID32442403
PMCPMC8187079
OpenAlexW3028521173

What OpenQuestion holds

Textmetadata
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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.