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Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer

GSE306515 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/09/03 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 3 × mPDAC1, RPMI, vehicle vs 3 × mPDAC1, RPMI, gemcitabine vs 3 × mPDAC1, TIFM, vehicle vs 3 × mPDAC1, TIFM, gemcitabineGroups 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
Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancerbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Cytotoxic chemotherapy remains the standard-of-care treatment for patients with pancreatic ductal adenocarcinoma (PDAC). However, chemotherapy only has modest effects at improving overall survival due to primary or rapidly acquired chemoresistance. The biological underpinnings of PDAC therapy resistance are incompletely defined, but the tumor microenvironment is known to be a major contributor to chemoresistance.
Read the full summary ↓
We have found chemoresistance is imprinted on PDAC cells by the tumor microenvironment and persists for a period of days after PDAC cells are removed from tumors. However, PDAC chemoresistance is lost upon long term culture in standard laboratory conditions. Interestingly, culture of PDAC cells in Tumor Interstitial Fluid Medium (TIFM), a culture medium we developed to recapitulate the nutrient availability of the tumor microenvironment, maintains PDAC cells in a chemoresistant state even after long term culture ex vivo. These findings suggest that microenvironmental metabolic stress keeps PDAC cells in a physiologically relevant, therapy resistant cell state that standard culture models fail to maintain. Using TIFM culture, we sought to understand how PDAC cells in this state resist chemotherapeutic challenge. We found that chemotherapy drugs largely retain on-target activity within TIFM medium but fail to activate cell death, enabling a “chemotolerant” cell state, which is also observed in PDAC tumors. This chemotolerant state is driven by suppression of apoptotic priming and can be overcome by targeting the anti-apoptotic regulator BCL-xL. Taken together, these findings suggest that reprogramming of cell death mechanisms by the PDAC nutrient microenvironment is a key contributor to therapy resistance in this disease.
Published in
Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer
Sheehan C, Hu L, Cognet G et al. · bioRxiv : the preprint server for biology 2025 · PMID 40964288 · doi:10.1101/2025.09.04.673818
This dataset
Open GSE306515 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 GSE306515_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 PRJNA1311024 and SRA study SRP613030. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40964288) ↗
Study design
3 × mPDAC1, RPMI, vehicle vs 3 × mPDAC1, RPMI, gemcitabine vs 3 × mPDAC1, TIFM, vehicle vs 3 × mPDAC1, TIFM, gemcitabine

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
Datasets on a similar topic

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