Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bidirectional crosstalk between cancer cells and cancer-associated fibroblasts in mixed organoid system elicits transcriptomic characteristics of pancreatic cancer with potential therapeutic vulnerabilities

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253561 | GEO | 2024/02/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Bidirectional crosstalk between cancer cells and cancer-associated fibroblasts in mixed organoid system elicits transcriptomic characteristics of pancreatic cancer with potential therapeutic vulnerabilities [scRNA-seq]

Project description:Pancreatic cancer's aggressiveness and poor response to conventional treatment have long necessitated a personalized medicine platform. Patient-derived pancreatic cancer organoids (PCOs) with matching genetic mutations have emerged as valuable tools for drug screening. However, PCOs, composed solely of cancer cells, may exhibit different characteristics from the original tumors due to the absence of the tumor microenvironment (TME). To address these issues, we extensively characterized the transcriptomic features of matched patient-derived mixed PCO-CAF systems, combining pancreatic cancer cells and cancer-associated fibroblasts (CAFs), compared to PCOs and the original tumors. The mixed PCO-CAF model closely resembled the patient tissue's transcriptomic traits, indicating its potential in reflecting the TME. Single-cell RNA sequencing revealed different cell populations in the mixed PCO-CAF system, including myofibroblast-like CAFs and inflammatory CAFs, influencing the essential features of cancer cells in the TME. Several growth factors and cytokines were identified in both the patient tissue and mixed PCO-CAFs, suggesting the importance of intercellular signaling communication. Importantly, disrupting these interactions could lead to antitumor responses. Given the cumulative implications of our dataset, the mixed PCO-CAF emerges as a clinically applicable paradigm for personalized therapeutics.

2024-02-28 | GSE253559 | GEO

2024-02-28 | GSE253558 | GEO

Project description:Bidirectional crosstalk between cancer cells and cancer-associated fibroblasts in mixed organoid system elicits transcriptomic characteristics of pancreatic cancer with potential therapeutic vulnerabilities

| PRJNA1066281 | ENA

| PRJNA1066285 | ENA

| PRJNA1066286 | ENA

Metabolic re-programming of pancreatic cancer mediated by CDK4/6 inhibition elicits unique vulnerabilities

Project description:Gene expression levels were determined with control or PD-0332991 treatment CAPAN2 Cells were subject to DMSO/ PD-0332991 treatment. RNA was harvested at 72 hours post treatment and analyzed on Illumina microarrays

2015-12-21 | E-GEOD-75979 | biostudies-arrayexpress

Passenger deletions generate therapeutic vulnerabilities in cancer.

Project description:Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.

| S-EPMC3712624 | biostudies-literature

The STING pathway: Therapeutic vulnerabilities in ovarian cancer.

Project description:Ovarian cancer is the leading cause of mortality due to gynecologic malignancy. The majority of women diagnosed with the most common subtype, high-grade serous ovarian carcinoma (HGSC), develop resistance to conventional therapies despite initial response to treatment. HGSC tumors displaying DNA damage repair (DDR) gene deficiency and high chromosomal instability mainly associate with higher cytotoxic immune cell infiltration and expression of genes associated with these immune pathways. Despite the high level of immune infiltration observed, the majority of patients with HGSC have not benefited from immunomodulatory treatments as the mechanistic basis of this infiltration is unclear. This lack of response can be primarily attributed to heterogeneity at the levels of both cancer cell genetic alterations and the tumour immune microenvironment. Strategies to enhance anti-tumour immunity have been investigated in ovarian cancer, of which interferon activating therapies present as an attractive option. Of the several type I interferon (IFN-1) stimulating therapies, exogenously activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is emerging as a promising avenue. Herein, we highlight our current understanding of how constitutive and induced cGAS-STING pathway activation influences the ovarian tumour microenvironment. We further elaborate on the links between the genomic alterations prevalent in ovarian tumours and how the resultant immune phenotypes can make them more susceptible to exogenous STING pathway activation and potentiate immune-mediated killing of cancer cells. The therapeutic potential of cGAS-STING pathway activation in ovarian cancer and factors implicating treatment outcomes are discussed, providing a rationale for future combinatorial treatment approaches on the backbone of chemotherapy.

| S-EPMC9381712 | biostudies-literature

Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities.

Project description:Due to loss of p16ink4a in pancreatic ductal adenocarcinoma (PDA), pharmacological suppression of CDK4/6 could represent a potent target for treatment. In PDA models, CDK4/6 inhibition had a variable effect on cell cycle but yielded accumulation of ATP and mitochondria. Pharmacological CDK4/6 inhibitors induce cyclin D1 protein levels; however, RB activation was required and sufficient for mitochondrial accumulation. CDK4/6 inhibition stimulated glycolytic and oxidative metabolism and was associated with an increase in mTORC1 activity. MTOR and MEK inhibitors potently cooperate with CDK4/6 inhibition in eliciting cell-cycle exit. However, MTOR inhibition fully suppressed metabolism and yielded apoptosis and suppression of tumor growth in xenograft models. The metabolic state mediated by CDK4/6 inhibition increases mitochondrial number and reactive oxygen species (ROS). Concordantly, the suppression of ROS scavenging or BCL2 antagonists cooperated with CDK4/6 inhibition. Together, these data define the impact of therapeutics on PDA metabolism and provide strategies for converting cytostatic response to tumor cell killing.

| S-EPMC4757440 | biostudies-literature

vulcanSpot: a tool to prioritize therapeutic vulnerabilities in cancer.

Project description:MotivationGenetic alterations lead to tumor progression and cell survival but also uncover cancer-specific vulnerabilities on gene dependencies that can be therapeutically exploited.ResultsvulcanSpot is a novel computational approach implemented to expand the therapeutic options in cancer beyond known-driver genes unlocking alternative ways to target undruggable genes. The method integrates genome-wide information provided by massive screening experiments to detect genetic vulnerabilities associated to tumors. Then, vulcanSpot prioritizes drugs to target cancer-specific gene dependencies using a weighted scoring system based on well known drug-gene relationships and drug repositioning strategies.Availability and implementationhttp://www.vulcanspot.org.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC6853644 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data