Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differential mRNA expression analysis of multiple human and mouse pancreatic cancer cells and tumors after DMSO, tazemetostat, RMC-6236, or the combination treatment.

ABSTRACT: Our study demonstrated that combined treatment with the EZH2 inhibitor tazemetostat and the KRAS inhibitor RMC-6236 significantly suppressed the growth of subcutaneous and orthotopic tumors. To investigates the transcriptional effects of combined EZH2 and KRAS inhibition in pancreatic cancer models, transcriptome profiling was performed in PSN1, SW1990, and KPC cells treated with DMSO, tazemetostat, RMC-6236, or the combination of both inhibitors. In parallel, orthotopic KPC tumors subjected to the same treatments were harvested for RNA sequencing. In addition, an acquired resistance model to RMC-6236 was established in mice, and tumors treated with RMC-6236 alone or in combination with tazemetostat were collected at different stages for RNA-seq analysis to characterize dynamic changes in gene expression profiles.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE315130 | GEO | 2026/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell RNA-seq analysis of immune microenvironment changes in pancreatic cancer following combined EZH2 and KRAS inhibition

Project description:Our study demonstrated that combined treatment with the EZH2 inhibitor tazemetostat and the KRAS inhibitor RMC-6236 significantly suppressed the growth of both subcutaneous and orthotopic tumors. To investigate changes in the tumor microenvironment following combined EZH2 and KRAS inhibition in pancreatic cancer, mice bearing subcutaneous KPC tumors were treated with vehicle, RMC-6236 alone, or RMC-6236 in combination with tazemetostat. CD45⁺ cells were isolated and subjected to 10× Genomics single-cell RNA sequencing.

2026-01-31 | GSE315131 | GEO

ChIP-seq analysis of H3K27ac changes in pancreatic cancer cells treated with EZH2 and KRAS inhibitors

Project description:Our study demonstrates that combined treatment with the EZH2 inhibitor tazemetostat and the KRAS inhibitor RMC-6236 markedly activates the expression of senescence-associated secretory phenotype (SASP) genes in pancreatic cancer, thereby enhancing the therapeutic efficacy of RMC-6236 and potentially providing a strategy to overcome resistance to KRAS inhibition. To characterize the epigenetic features underlying SASP gene activation, H3K27ac ChIP-seq was performed in PSN1 cells treated with DMSO, tazemetostat, RMC-6236, or the combination of both inhibitors.

2026-01-31 | GSE315129 | GEO

Differential mRNA expression analysis of multiple human and mouse pancreatic cancer cells and tumors after DMSO, tazemetostat, RMC-6236, or the combination treatment.

Project description:Differential mRNA expression analysis of multiple human and mouse pancreatic cancer cells and tumors after DMSO, tazemetostat, RMC-6236, or the combination treatment.

| PRJNA1395035 | ENA

Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Project description:Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

| 2731011 | ecrin-mdr-crc

The EZH2 inhibitor tazemetostat mitigates HIV immune evasion, reduces reservoir formation, and promotes durable CD8⁺ T-cell revitalization

Project description:Persistent HIV reservoirs in CD4⁺ T-cells impede efforts to cure HIV infection. We identified overexpression of enhancer of zeste homolog 2 (EZH2) in HIV-infected CD4⁺ T-cells that survive cytotoxic T lymphocyte (CTL) exposure, suggesting a mechanism of CTL resistance. Inhibition of EZH2 with the FDA-approved drug tazemetostat increased surface expression of major histocompatibility complex class I (MHC-I) on CD4⁺ T-cells, counteracting HIV Nef–mediated MHC-I downregulation. This enhancement improved CTL-mediated elimination of HIV-infected cells and suppressed viral replication in vitro. In a participant-derived xenograft mouse model, tazemetostat elevated MHC-I and the pro-apoptotic protein BIM in CD4⁺ T-cells, facilitating CD8⁺ T-cell–mediated reduction of HIV reservoir seeding. Additionally, tazemetostat promoted sustained skewing of CD8⁺ T-cells toward less differentiated and less exhausted phenotypes. Our findings reveal EZH2 overexpression as a novel mechanism of CTL resistance and support the clinical evaluation of tazemetostat to enhance immune-mediated clearance of HIV reservoirs.

2026-01-26 | PXD061146 | Pride

Tumor-selective effects of active RAS inhibition in pancreatic ductal adenocarcinoma

Project description:Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS, we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models, including human and murine cell lines, patient-derived organoids, human PDAC explants, subcutaneous and orthotopic cell-line or patient-derived xenografts, syngeneic allografts, and genetically engineered mouse models. We observed broad and pronounced anti-tumor activity across these models following direct RAS inhibition at doses and concentrations that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS inhibition in the setting of PDAC.

2024-03-15 | PXD047878 | Pride

Renal medullary carcinomas (RMC) habor a distinct methylation phenotype

Project description:Renal medullary carcinomas (RMC) are rare aggressive tumors of the kidneys, characterized by a -mostly- biallelic loss of SMARCB1. Characteristically, these tumors arise in patients with sickle cell trait or other hemoglobinopathies. Recent molecular and landscaping characterization efforts have unraveled oncogenic pathways that drive tumorigenesis. Among these, gene sets that characterize replicative stress and the innate immune response are upregulated in RMCs. Despite comprehensive genetic and transcriptomic characterizations, commonalities or differences to other SMARCB1 deficient entities so far have not been investigated. We analyzed the methylome of four novel primary RMC and compared it to other, SMARCB1 deficient entities such as rhabdoid tumors (RT) and epithelioid sarcomas using 850K methylation arrays. In accordance with previous gene expression data, we find that RMCs separate from other SMARCB1 deficient entities such as extra-and intracranial rhabdoid tumors, pointing to a potentially different cell of origin and a role of additional mutations or genetic aberrations that may drive tumorigenesis and thus alter the methylome when compared to rhabdoid tumors. In a focused analysis of genes that are important for nephrogenesis, we detected particularly genes that govern early nephrogenesis such as FOXI to be hypomethylated and expressed at high levels in RMC. Overall, our analyses underscore the fact that RMCs represent a separate entity with limited similarities to rhabdoid tumors warranting specific treatment, tailored to the aggressiveness of the disease.

2022-11-02 | GSE211942 | GEO

Study of RMC-9805 in Participants With KRASG12D-Mutant Solid Tumors

Project description:This study is to evaluate the safety and tolerability of RMC-9805 in adults with KRAS G12D-mutant solid tumors.

| 92209 | ecrin-mdr-crc

RAS(ON) multi-selective inhibition drives anti-tumor immunity in preclinical models of NRAS-mutant melanoma

Project description:Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. Here, we demonstrate that RMC-7977, a preclinical RAS(ON) multi-selective inhibitor respresentative of the investigational agent daraxonrasib (RMC-6236), elicits potent anti-tumor immune responses across several NRAS-mutant melanoma models. Treatment with RMC-7977 led to rapid tumor regressions driven by inhibition of MAPK signaling, upregulation of MHC and PD-L1 proteins, and enhanced infiltration of CD4⁺ and CD8⁺ T cells. Complete responses was dependent on adaptive immunity, as both CD4⁺ and CD8⁺ T cells were essential for extended survival. Resistance to treatment was marked by reduced T cell infiltration, loss of MHCI expression, and expansion of MDSCs. Combining RMC-7977 with anti-PD-1 boosted T cytotoxic cell infiltration, reprogrammed myeloid cells toward an antigen-presenting phenotype, and improved survival in models resistant to PD-1 blockade. Notably, objective clinical responses were observed in two NRAS-mutant melanoma patients treated with daraxonrasib (RMC-6236) in an ongoing phase I/Ib clinical trial.

2025-10-22 | GSE300712 | GEO

Muscle and adipose transcriptome in a mouse model of cachexia induced by orthotopic pancreatic cancer, with and without tumor-derived interleukin-6 (IL-6)

Project description:Pancreatic ductal adenocarcinoma (PDAC) causes involuntary wasting of adipose and muscle tissue, also known as cachexia. Cachexia is a major cause of cancer-related deaths, particularly among patients with PDAC. Here we profiled gene expression in adipose tissue and skeletal muscle in normal/sham control mice and in mice bearing orthotopic PDAC tumors. PDAC tumors were initiated by intra-pancreatic injection of a cell line derived from the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of pancreatic cancer, or by injection of the same cell line deleted for the IL6 gene using CRISPR/Cas9. KPC-IL6 knockout (ko) cells caused less adipose wasting and no muscle loss compared with KPC-wildtype (wt) cells.

2021-04-07 | GSE123310 | GEO

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