Dataset Information

Characterizing the transcriptome of WT organoids, RXRi organoids and APCko tumoroids

ABSTRACT: Characterizing the transcriptome of WT organoids, RXRi organoids and APCko tumoroids

PROVIDER: PRJNA1000920 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR25474518.fastq.gz	Fastqsanger.gz
	SRR25474519.fastq.gz	Fastqsanger.gz
	SRR25474520.fastq.gz	Fastqsanger.gz
	SRR25474521.fastq.gz	Fastqsanger.gz
	SRR25474522.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 9

Similar Datasets

Project description:Purpose: Advanced high-grade gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) are highly aggressive and heterogeneous epithelial malignancies with poor clinical outcomes. No therapeutic predictive biomarkers exist and representative preclinical models to study their biology are missing. Patient-derived (PD) tumoroids may enable fast ex vivo pharmacotyping and provide subsidiary biological information for more personalized therapy strategies in individual patients. Experimental Design: PD tumoroids were established from rare biobanked surgical resections of advanced high-grade GEP-NEN patients. Using targeted in vitro pharmacotyping and next-generation sequencing of patient samples and matching PD tumoroids, we profiled individual patients and compared treatment-induced molecular stress response and in vitro drug sensitivity to the clinical therapy response. Results: We demonstrate high success rates in culturing PD tumoroids of high-grade GEP-NENs within clinically meaningful timespans. PD tumoroids recapitulate biological key features of high-grade GEP-NEN and mimic clinical response to cisplatin and temozolomide in vitro. Moreover, investigating treatment-induced molecular stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A (KDM5A) and interferon-beta (IFNB1) as two vulnerabilities that act synergistically in combination with cisplatin and may present novel therapeutic options in high-grade GEP-NENs. Conclusion: Patient-derived tumoroids from high-grade GEP-NENs represent a relevant model to screen drug sensitivities of individual patients within clinically relevant timespans and provide novel functional insights into drug-induced stress responses. Clinical patient response to standard-of-care chemotherapeutics matches with drug sensitivities of PD tumoroids. Together, our findings provide a functional precision oncology approach for gathering patient-centered subsidiary treatment information that will potentially increase therapeutic opportunities in the framework of personalized medicine.

Dataset Information

Characterizing the transcriptome of WT organoids, RXRi organoids and APCko tumoroids

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets