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Mechanisms of resistance to oncogenic KRAS inhibition in pancreatic cancer

GSE269985 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2024/06/17 Platform GPL24676Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Topic
Pancreatic cancerThis series is part of our curated briefing on it.
Samples
30 samples: 10 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic CancerCancer discovery · 2024
Summary (written by the submitters)
KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy.
Read the full summary ↓
MRTX1133 treatment of the KrasLSL-G12D/+;Trp53LSL-R172H/+;p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, and Cdk6/Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. Moreover, in KPC and PDX models, mesenchymal and basal-like cell states displayed increased response to KRAS inhibition compared to the classical state. Combination treatment with KRASG12D inhibition and chemotherapy significantly improved tumor control in PDAC mouse models. Collectively, these data elucidate co-evolving resistance mechanisms to KRAS inhibition and support multiple combination therapy strategies.
Published in
Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer
Dilly J, Hoffman MT, Abbassi L et al. · Cancer discovery 2024 · PMID 38975874 · doi:10.1158/2159-8290.CD-24-0177
This dataset
Open GSE269985 in finder → Find more RNA-seq datasets → Pancreatic cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269985_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1124557 and SRA study SRP514229. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38975874) ↗
Study design
10 conditions, mostly in triplicate
Panc 02.03 parental ×3 PANC-1 parental ×3 PANC-1 MRTX1133 resistant, ×3 6694C2 parental ×3 6694C2 MRTX1133 resistant, ×3 6499C4 parental ×3 6499C4 MRTX1133 resistant, ×3 6419C5 parental ×3 +3 more

Supports a between-group comparison across 29 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 29 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Pancreatic cancer datasets

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