Colorectal cancer organoid models uncover oxaliplatin-resistant mechanisms at single cell resolution

Chen, Guanglong; Gong, Ting; Wang, Zhe; Wang, Zeyu; Lin, Xiaolin; Chen, Sunrui; Sun, Chao; Zhao, Weijie; Kong, Ye; Ai, Huihan; Yang, Hang; Liu, Yusheng; Wu, Fangyan; Kang, Jiawei; Zhao, Shasha; Xiao, Xiuying; Sun, Jing Ping; He, Aina; Li, Zhi

doi:10.1007/s13402-022-00705-5

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…However, they failed to predict the outcome of 5-FU and oxaliplatin, and failed to identify patients who may benefit from treatment. Chen et al ( 96 ) administered different concentrations of 5-FU and oxaliplatin to CRC organoids to investigate drug susceptibility and the test data were consistent with clinical data. Then, through single-cell sequencing technology, it was speculated that driver genes Stathmin 1, vascular endothelial growth factor A and N-myc downstream-regulated gene 1 and transcription factors [E2F transcription factor 1, breast cancer susceptibility gene 1, MYB proto-oncogene like 2, caudal-type homeobox 1 (CDX1) and CDX2] were potential oxaliplatin resistance targets ( 96 ).…”

Section: Organoids In the Treatment Of Crcmentioning

confidence: 87%

“…Chen et al ( 96 ) administered different concentrations of 5-FU and oxaliplatin to CRC organoids to investigate drug susceptibility and the test data were consistent with clinical data. Then, through single-cell sequencing technology, it was speculated that driver genes Stathmin 1, vascular endothelial growth factor A and N-myc downstream-regulated gene 1 and transcription factors [E2F transcription factor 1, breast cancer susceptibility gene 1, MYB proto-oncogene like 2, caudal-type homeobox 1 (CDX1) and CDX2] were potential oxaliplatin resistance targets ( 96 ). Lv et al ( 97 ) used locally advanced rectal cancer organoids to observe whether the sensitivity of irinotecan could predict complete response and survival.…”

Section: Organoids In the Treatment Of Crcmentioning

confidence: 87%

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Tumor organoid model of colorectal cancer (Review)

Yang,

Xiao,

Wang

et al. 2023

Oncol Lett

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The establishment of self-organizing ‘mini-gut’ organoid models has brought about a significant breakthrough in biomedical research. Patient-derived tumor organoids have emerged as valuable tools for preclinical studies, offering the retention of genetic and phenotypic characteristics of the original tumor. These organoids have applications in various research areas, including in vitro modelling, drug discovery and personalized medicine. The present review provided an overview of intestinal organoids, focusing on their unique characteristics and current understanding. The progress made in colorectal cancer (CRC) organoid models was then delved into, discussing their role in drug development and personalized medicine. For instance, it has been indicated that patient-derived tumor organoids are able to predict response to irinotecan-based neoadjuvant chemoradiotherapy. Furthermore, the limitations and challenges associated with current CRC organoid models were addressed, along with proposed strategies for enhancing their utility in future basic and translational research.

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Section: Organoids In the Treatment Of Crcmentioning

confidence: 87%

Section: Organoids In the Treatment Of Crcmentioning

confidence: 87%

Tumor organoid model of colorectal cancer (Review)

Yang,

Xiao,

Wang

et al. 2023

Oncol Lett

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“…Ligand-receptor analysis-a method that infers a list of possible ligand-receptor pairs between two cell populations from single-cell gene expression data as an indicator of cell-cell interactions-showed enrichment of unique interactions that differed between the drug-responsive and drugresistant PDOs, which may be an interesting basis for future study of resistance. [200] Finally, Zhao et al integrated both trajectory and ligand-receptor analyses in a study of hepatobiliary tumor PDOs to identify cells that may sustain PDO growth and highlight interactions between cells along different trajectories that may contribute to drug resistance. [201] These studies demonstrate how single cell technologies can be used to elucidate biological mechanisms underpinning tumor cell heterogeneity that cannot be efficiently explored with bulk experimental techniques.…”

Section: Single Cell Analysis Of Pdos In Conventional Culture Setupsmentioning

confidence: 99%

Exploring New Dimensions of Tumor Heterogeneity: The Application of Single Cell Analysis to Organoid‐Based 3D In Vitro Models

Landon‐Brace,

Li,

McGuigan

2023

Adv Healthcare Materials

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Modelling the heterogeneity of the tumor microenvironment (TME) in vitro is essential to investigating fundamental cancer biology and developing novel treatment strategies that holistically address the factors affecting tumor progression and therapeutic response. Thus, the development of new tools for both in vitro modelling, such as patient‐derived organoids (PDOs) and complex 3D in vitro models, and single cell omics analysis, such as single‐cell RNA‐sequencing, represents a new frontier for investigating tumor heterogeneity. Specifically, the integration of PDO‐based 3D in vitro models and single cell analysis offers a unique opportunity to explore the intersecting effects of interpatient, microenvironmental, and tumor cell heterogeneity on cell phenotypes in the TME. In this review, we discuss the current use of PDOs in complex 3D in vitro models of the TME and highlight emerging directions in the development of these models. Next, we examine work that has successfully applied single cell analysis to PDO‐based models and identify important experimental considerations for this approach. Finally, we highlight open questions that may be amenable to exploration using the integration of PDO‐based models and single cell analysis. Ultimately, such investigations may facilitate the identification of novel therapeutic targets for cancer that address the significant influence of tumor‐TME interactions.This article is protected by copyright. All rights reserved

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