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

Publication ,  Journal Article
Tung, K-L; Chen, K-Y; Negrete, M; Chen, T; Safi, A; Aljamal, AA; Song, L; Crawford, GE; Ding, S; Hsu, DS; Shen, X
Published in: Genes Dis
March 2021

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.

Duke Scholars

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Published In

Genes Dis

DOI

EISSN

2352-3042

Publication Date

March 2021

Volume

8

Issue

2

Start / End Page

203 / 214

Location

Netherlands
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tung, K.-L., Chen, K.-Y., Negrete, M., Chen, T., Safi, A., Aljamal, A. A., … Shen, X. (2021). Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance. Genes Dis, 8(2), 203–214. https://doi.org/10.1016/j.gendis.2019.10.012
Tung, Kuei-Ling, Kai-Yuan Chen, Marcos Negrete, Tianyi Chen, Alexias Safi, Abed Alhalim Aljamal, Lingyun Song, et al. “Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance.Genes Dis 8, no. 2 (March 2021): 203–14. https://doi.org/10.1016/j.gendis.2019.10.012.
Tung, Kuei-Ling, et al. “Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance.Genes Dis, vol. 8, no. 2, Mar. 2021, pp. 203–14. Pubmed, doi:10.1016/j.gendis.2019.10.012.
Tung K-L, Chen K-Y, Negrete M, Chen T, Safi A, Aljamal AA, Song L, Crawford GE, Ding S, Hsu DS, Shen X. Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance. Genes Dis. 2021 Mar;8(2):203–214.
Journal cover image

Published In

Genes Dis

DOI

EISSN

2352-3042

Publication Date

March 2021

Volume

8

Issue

2

Start / End Page

203 / 214

Location

Netherlands