GEO series

Drug Screening in 3D Microtumors Reveals DDR1/2-MAPK12-GLI1 as a Vulnerability in Cancer-Associated Fibroblasts

GSE304108 Mus musculus (mouse) RNA-seq (gene expression) 29 samples Submitted 2025/08/04 Platform GPL16791Platform GPL17021

At a glance

RNA-seq (gene expression) · mouse · 29 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: 29 samples: 14 conditions, mostly in duplicateGroups 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: Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblastsCell reports. Medicine · 2025

Summary (written by the submitters)

Interactions between cancer cells and surrounding stromal cells are critical for tumor biology and treatment response. We compare drug screening results from conventional 2D cancer cell lines with 3D tumor tissues and find that, on average, three times more drugs are effective in 3D microtumors. We confirmed the effectiveness of doramapimod, a compound that reduces 3D microtumor viability and suppresses tumor growth in mouse models, has no effect on cancer cell growth in monolayers.

Read the full summary ↓

Mechanistically, doramapimod targets DDR1/2 and MAPK12 kinases in cancer-associated fibroblasts (CAFs), decreasing extracellular matrix (ECM) production and enhancing interferon signaling. These kinases regulate ECM through GLI1 activity in CAFs, independently of canonical hedgehog signaling. Inhibiting the DDR1/2-MAPK12-GLI axis enhances the effectiveness of chemotherapy and immunotherapy in patient tumor slices and preclinical models. These findings highlight the importance of DDR1/2-MAPK12-GLI axis in CAF function and demonstrate the utility of 3D tissue models in identifying microenvironment-specific therapeutic targets.

Published in

Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts

Nishida-Aoki N, Zhu S, Chan M et al. · Cell reports. Medicine 2025 · PMID 40975064 · doi:10.1016/j.xcrm.2025.102357

This dataset

Open GSE304108 in finder → Find more 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 GSE304108_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 PRJNA1298926 and SRA study SRP604732. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40975064) ↗

Study design

14 conditions, mostly in duplicate

E0771 Doramapimod Treated RNA ×3 KPC1 Vehicle Control RNA ×2 KPC1 Doramapimod Treated RNA ×2 E0771 Vehicle Control RNA ×2 Breast CAFs DMSO RNA ×2 Breast CAFs Doramapimod High RNA ×2 Breast CAFs DDR1/2, MAPK12 Non-targeting Cont… ×2 Breast CAFs DDR1 Knockdown RNA ×2 +6 more

Supports a case/control comparison: 15 samples read as cases, 12 as controls.

How we read this: 14 replicated groups read from 29 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

GSM9143690 KPC1 Vehicle Control RNA Replicate 1 KPC1 Vehicle Control RNA
GSM9143691 KPC1 Vehicle Control RNA Replicate 2 KPC1 Vehicle Control RNA
GSM9143692 KPC1 Doramapimod Treated RNA Replicate 1 KPC1 Doramapimod Treate…
GSM9143693 KPC1 Doramapimod Treated RNA Replicate 2 KPC1 Doramapimod Treate…
GSM9143694 E0771 Vehicle Control RNA Replicate 1 E0771 Vehicle Control R…
GSM9143695 E0771 Vehicle Control RNA Replicate 2 E0771 Vehicle Control R…
GSM9143696 E0771 Doramapimod Treated RNA Replicate 1 E0771 Doramapimod Treat…
GSM9143697 E0771 Doramapimod Treated RNA Replicate 2 E0771 Doramapimod Treat…
GSM9143698 E0771 Doramapimod Treated RNA Replicate 3 E0771 Doramapimod Treat…
GSM9143699 Breast CAFs DMSO RNA Replicate 1 Breast CAFs DMSO RNA
GSM9143700 Breast CAFs DMSO RNA Replicate 2 Breast CAFs DMSO RNA
GSM9143701 Breast CAFs Doramapimod High RNA Replicate 1 Breast CAFs Doramapimod…
GSM9143702 Breast CAFs Doramapimod High RNA Replicate 2 Breast CAFs Doramapimod…
GSM9143703 Breast CAFs DDR1/2, MAPK12 Non-targeting Control RNA Replicate 1 Breast CAFs DDR1/2, MAP…
GSM9143704 Breast CAFs DDR1/2, MAPK12 Non-targeting Control RNA Replicate 2 Breast CAFs DDR1/2, MAP…
GSM9143705 Breast CAFs DDR1 Knockdown RNA Replicate 1 Breast CAFs DDR1 Knockd…
GSM9143706 Breast CAFs DDR1 Knockdown RNA Replicate 2 Breast CAFs DDR1 Knockd…
GSM9143707 Breast CAFs DDR2 Knockdown RNA Replicate 1 Breast CAFs DDR2 Knockd…
GSM9143708 Breast CAFs DDR2 Knockdown RNA Replicate 2 Breast CAFs DDR2 Knockd…
GSM9143709 Breast CAFs MAPK12 Knockdown RNA Replicate 1 Breast CAFs MAPK12 Knoc…
GSM9143710 Breast CAFs MAPK12 Knockdown RNA Replicate 2 Breast CAFs MAPK12 Knoc…
GSM9143711 Breast CAFs DMSO Replicate 1 Breast CAFs DMSO
GSM9143712 Breast CAFs DMSO Replicate 2 Breast CAFs DMSO
GSM9143713 Breast CAFs Gant61 Treated RNA Replicate 1 Breast CAFs Gant61 Trea…
GSM9143714 Breast CAFs Gant61 Treated RNA Replicate 2 Breast CAFs Gant61 Trea…
GSM9143715 Pancreas CAFs DMSO Replicate 1 Pancreas CAFs DMSO
GSM9143716 Pancreas CAFs DMSO Replicate 2 Pancreas CAFs DMSO
GSM9143717 Pancreas CAFs Gant61 Treated RNA Replicate 1 Pancreas CAFs Gant61 Tr…
GSM9143718 Pancreas CAFs Gant61 Treated RNA Replicate 2 Pancreas CAFs Gant61 Tr…

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.