Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

ABSTRACT: Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

PROVIDER: PRJNA1002299 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

Project description:KRAS G12C inhibitors (G12Ci) alone and in various combinations are being tested in multiple tumors with over-activation of the RAS/ERK pathway. KRAS plays a critical role in normal cell signaling; hence, G12Cis has been reported to create resistance. We found several novel pathways, including Hippo pathways, are enriched from significant dropouts upon MRTX849 treatment. Our results argue for testing KRAS G12C and TEAD inhibitor combinations in NSCLC patients.

2023-09-11 | GSE240110 | GEO

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy

Project description:Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy

| PRJNA1002303 | ENA

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [scRNA-seq]

Project description:KRAS G12C inhibitors (G12Ci) alone and in various combinations are being tested in multiple tumors with over-activation of the RAS/ERK pathway. KRAS plays a critical role in normal cell signaling; hence, G12Cis could influence the signaling pathways. We found that several novel pathways including Hippo pathways are upregulated upon MRTX849 treatment. Our results argue for testing KRAS G12C and TEAD inhibitor combinations in NSCLC patients.

2023-09-11 | GSE240118 | GEO

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [RNA-seq-mm10]

Project description:KRAS G12C inhibitors (G12Ci) alone and in various combinations are being tested in multiple tumors with over-activation of the RAS/ERK pathway. KRAS plays a critical role in normal cell signaling; hence, G12Cis could influence the signaling pathways. We found that several novel pathways including Hippo pathways are upregulated upon MRTX849 treatment. Our results argue for testing KRAS G12C and TEAD inhibitor combinations in NSCLC patients.

2023-09-11 | GSE240113 | GEO

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [scRNA-seq]

Project description:Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [scRNA-seq]

| PRJNA1002309 | ENA

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [RNA-seq-mm10]

Project description:Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [RNA-seq-mm10]

| PRJNA1002301 | ENA

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [RNA-seq-human]

Project description:Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [RNA-seq-human]

| PRJNA1002298 | ENA

SHP2 Inhibition Abrogates Adaptive Resistance to KRAS-G12C-Inhibition and Remodels the Tumor Microenvironment of KRAS-Mutant Tumors

Project description:KRAS is the most frequently mutated oncogene in human cancer, and KRAS inhibition has been a longtime goal. Recently, inhibitors (G12C-Is) that bind KRAS-G12C-GDP and react with Cys-12 were developed. Using new affinity reagents to monitor KRAS-G12C activation and inhibitor engagement, we found that SHP2 inhibitors (SHP2-Is) increased KRAS-GDP occupancy, enhancing G12C-I efficacy. SHP2-Is abrogated feedback signaling by multiple RTKs and adaptive resistance to G12C-Is in vitro, in xenografts, and in syngeneic KRAS-G12C-mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) models. The combination of SHP2-I and G12C-I evoked favorable changes in the immune microenvironment, decreasing myeloid suppressor cells, increasing CD8+ T cells, and sensitizing tumors to PD-1 blockade. Experiments using an inhibitor-resistant SHP2 mutant showed that SHP2 inhibition in PDAC cells is required for tumor regression and remodeling of the immune microenvironment, but SHP2-Is also had direct effects on angiogenesis. Our results demonstrate that SHP2-I/G12C-I combinations confer a substantial survival benefit in PDAC and NSCLC and identify additional potential combination strategies. G12C-Is show significant, but limited, efficacy as single agents, in part because of “adaptive resistance”. We find that combining G12C-Is with SHP2-Is abrogates adaptive resistance and results in favorable changes in the immune microenvironment that potentiate PD-1 blockade in KRAS-mutant malignancies. SHP2-Is also can have direct, context-dependent, effects on tumor vasculature.

2020-10-01 | GSE149815 | GEO

Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor

Project description:We report RNAseq gene expression data following ARS-1620 treatment and shKRAS expressing cells (NCI-H358). We also compare gene expression changes following treatment with ARS-1620 or trametinib in NCI-H358, LU65 (KRAS-G12C+), and A549 (KRAS-G12S+) cells. Additionally we report a time course (4, 24, 48hr) of ARS-1620 and trametinib treated NCI-H358 cells.

2018-01-24 | GSE103021 | GEO

Transcriptomic characterization of sotorasib-resistant tumors in Kras-G12C/Trp53-driven LUAD in genetically engineered mice

Project description:To characterize sotorasib resistance in lung adenocarcinomas (LUAD), we generated genetically engineered mice (Kras-G12C, Trp53-KO) and compared the transcriptional profiles of untreated and sotorasib-resistant tumors

2023-03-05 | GSE204752 | 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