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CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRASG12D inhibition in pancreatic ductal adenocarcinoma (spatial)

GSE269680 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2025/12/02 Platform GPL19057Platform GPL30172Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 15 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)
Samples
15 samples: 5 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
CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRAS (G12D) inhibition in pancreatic ductal adenocarcinomabioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Mutations in KRAS are a dominant driver of pancreatic ductal adenocarcinoma (PDAC), with over 40% of PDAC patients presenting with KRASG12D mutations. The recent development of small molecule inhibitors targeting KRASG12D, has enabled effective targeting of mutant KRAS signaling and suppression of PDAC; however, the contribution of the tumor microenvironment (TME) to the therapeutic efficacy of KRASG12D inhibition and mechanism/s of resistance to KRASG12D suppression remain to be elucidated.
Read the full summary ↓
Here, we employed spatial transcriptomics and CODEX-based spatial proteomics to evaluate cancer cell intrinsic and extrinsic responses to KRASG12D inhibition with MRTX1133. MRTX1133 treatment was associated with increased CD11c+ cells, T cells, and tumor-restraining fibroblasts within proximity to cancer cells, suggesting that antigen presentation and remodeling of the local microenvironment is associated with an effective response to KRASG12D inhibition. In the context of emergence of MRTX1133 therapy resistance, CDK8, a multiprotein mediator complex associated kinase, was identified as a mediator of resistance in part through induction of downstream CXCL2 chemokine secretion, inhibition of FAS expression, and remodeling of the TME to promote immune evasion. Targeting CDK8 in combination with aCTLA-4 immunotherapy overcomes resistance to small molecule mediated targeted KRASG12D inhibition with prolonged survival of mice with PDAC.
Published in
CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRAS (G12D) inhibition in pancreatic ductal adenocarcinoma
McAndrews KM, Mahadevan KK, Li B et al. · bioRxiv : the preprint server for biology 2025 · PMID 40791564 · doi:10.1101/2025.01.29.635543
This dataset
Open GSE269680 in finder → Find more mouse RNA-seq datasets →
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 GSE269680_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 PRJNA1123237 and SRA study SRP513547. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40791564) ↗
Study design
5 conditions, mostly in triplicate
C57 HY19636 isotype/vehicle ×3 C57 HY19636 MRTX1133 sensitive ×3 C57 HY19636 MRTX1133 resistant ×3 KC vehicle ×3 KC MRTX1133 ×3

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 15 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
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