Evidence map›Paper›PMID 33997167›Full record

ArticleGenes & diseases2021

Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance.

Kuei-Ling Tung, Kai-Yuan Chen, Marcos Negrete, Tianyi Chen, Alexias Safi, Abed Alhalim Aljamal, Lingyun Song, Gregory E Crawford, Shengli Ding, David S Hsu and 1 more

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

Article in Genes & diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 2 pooled it
0.7field-weighted citation impact, top 26% 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

17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

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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

11 authors at 4 institutions in 1 country.

Kuei-Ling TungDepartment of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA.
Kai-Yuan ChenDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Marcos NegreteDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Tianyi ChenDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Alexias SafiCenter for Genomics and Computational Biology, Duke University, Durham, NC, 27708, USA.
Abed Alhalim AljamalDepartment of Medical Oncology, Duke University Medical Center, Durham, NC, 27708, USA.
Lingyun SongDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, 27708, USA.
Gregory E CrawfordCenter for Genomics and Computational Biology, Duke University, Durham, NC, 27708, USA.
Shengli DingDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
David S HsuCenter for Genomics and Computational Biology, Duke University, Durham, NC, 27708, USA.
Xiling ShenDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Duke University · USPratt Institute · USDuke Medical Center · USCornell University · US

Funding

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 U01 CA214300NCI NIH HHS U01 CA217514
6 · The paper itself

Abstract

Colorectal cancer is a leading cause of cancer deaths. Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies. Here, we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment. Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression. CRISPR/Cas9 silencing of fibroblast growth factor receptor 1 (FGFR1) and oxytocin receptor (OXTR) helped overcome oxaliplatin resistance. Similarly, treatment with oxaliplatin in combination with an FGFR1 inhibitor (PD166866) or an antagonist of OXTR (L-368,899) suppressed chemoresistant organoids. However, oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid, suggesting that chromatin accessibility changes are patient-specific. The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.

Indexed as

Chromatin accessibilityDrug screeningPatient-derived organoidsPersonalized medicineTarget discovery

Identifiers

PMID33997167
PMCPMC8099686
OpenAlexW2982608828

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.