Evidence map›Paper›PMID 38380561›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar and 19 more

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

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  9. Review
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

29 authors at 6 institutions in 3 countries.

Kun XiangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.ORCID 0000-0001-7793-4352
Ergang WangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
John MantyhDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Gabrielle RupprechtDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Marcos NegreteDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Golshid SanatiDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Carolyn HsuDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Peggy RandonLaboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA.
Anders DohlmanDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Kai KretzschmarOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, Utrecht, CT, 3584, The Netherlands.
Shree BoseDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Nicholas GirouxDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Shengli DingDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Lihua WangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Jorge Prado BalcazarDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Qiang HuangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Pasupathi SundaramoorthyDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Rui XiDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Shannon Jones McCallDepartment of Pathology, School of Medicine, Duke University, Durham, NC, 27710, USA.
Zhaohui WangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Chongming JiangTerasaki Institute, Los Angeles, CA, 90024, USA.
Yubin KangDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Scott KopetzDepartment of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Gregory E CrawfordDepartment of Pediatrics, Division of Medical Genetics, School of Medicine, Duke University, Durham, NC, 27710, USA.
Steven M LipkinDepartment of Medicine and Program in Mendelian Genetics, Weill Cornell Medicine, New York, NY, 10021, USA.
Xiao-Fan WangDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA.
Hans CleversOncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, Utrecht, CT, 3584, The Netherlands.
David HsuDepartment of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA.
Xiling ShenDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.ORCID 0000-0002-4978-3531
Duke University · USRoyal Netherlands Academy of Arts and Sciences · NLCornell University · USNational Institute of Environmental Health Sciences · USTerasaki Foundation · USThe University of Texas MD Anderson Cancer Center · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Robust Control of the Stem Cell NicheR35GM122465 · NIGMS · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · PI Xiling Shen · 2017 to 2026
$5.6M
Cooperative Human Tissue Network Support through Duke's BioRepository & Precision Pathology CenterUM1CA239755 · NCI · DUKE UNIVERSITY · PI Shannon Jones McCall · 2019 to 2026
$5.4M
An organotypic model recapitulating colon cancer microenvironment and metastasisU01CA214300 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, EMINA HUI-NA, SHEN, XILING · 2017 to 2021
$3.1M
Epigenomic Reprogramming in Patient Derived Models of Colorectal CancerU01CA217514 · NCI · DUKE UNIVERSITY · PI HSU, SHIAOWEN DAVID · 2018 to 2022
$3.1M
NCI NIH HHS P30 CA014236NCI NIH HHS U01 CA214300NCI NIH HHS U01CA214300NCI NIH HHS U01 CA217514NCI NIH HHS U01CA217514NCI NIH HHS UM1 CA239755NIGMS NIH HHS R35 GM122465NIGMS NIH HHS R35GM122465
6 · The paper itself

Abstract

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Indexed as

Chromatin Assembly and DisassemblyColorectal NeoplasmsOrganoidsAnimalsDisease Models, AnimalHumansMiceATAC‐seq, Colorectal Cancer (CRC)Patient‐Derived Models of Cancer (PDMC)Patient‐Derived Organoids (PDO)Patient‐Derived Xenografts (PDX)

Identifiers

PMID38380561
PMCPMC11040356
OpenAlexW4392013294

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.