GEO series
A RAS(ON) multi-selective inhibitor combination therapy triggers long-term tumor control through senescence-associated tumor-immune equilibrium in preclinical models of PDAC
GSE293456
Mus musculus (mouse)
RNA-seq (gene expression)
30 samples
Submitted 2025/04/07
Platform GPL34290
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)
- Samples
- 30 samples: 27 distinct titles, 3 of them repeatedGroups 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
- A RAS(ON) Multi-Selective Inhibitor Combination Therapy Triggers Long-term Tumor Control through Senescence-Associated Tumor-Immune Equilibrium in Pancreatic Ductal AdenocarcinomaCancer discovery · 2025
Summary (written by the submitters)
Pharmacological inhibition of oncogenic RAS represents an attractive strategy to target pancreatic ductal adenocarcinoma (PDAC), an almost ubiquitously RAS-driven disease. However, initial responses to targeted monotherapy inhibition of active RAS can be followed by relapses, potentially driven by the persistence of drug-tolerant tumor cells.
Read the full summary ↓
To target these ‘persister’ cells, we investigated strategies to increase their immune visibility in mouse models of PDAC. We show that combining a RAS(ON) multi-selective inhibitor with the CDK4/6 inhibitor palbociclib drives persister cells into a senescent-like state, which coincides with improved tumor control and substantial remodeling of the tumor microenvironment. Combining RAS(ON) and CDK4/6 inhibition with a CD40 agonist results in durable regressions and CD4 T cell-dependent tumor-immune equilibrium. Our studies reveal a combinatorial approach that circumvents resistance to RAS(ON) inhibitor monotherapy in preclinical models and demonstrate a mechanism by which therapy-induced senescence can be reinforced by the immune system, resulting in durable tumor control.
Published in
Broderick C, Mezzadra R, Sisso EM et al.
· Cancer discovery 2025
· PMID 40299790
· doi:10.1158/2159-8290.CD-24-1425
This dataset
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.
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 GSE293456_RAW.tar (it can run to tens of gigabytes).
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.
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 PRJNA1244740 and SRA study SRP575757. Searching any of these in the dataset finder brings you back here.
Study design
27 distinct titles, 3 of them repeated
KPC treated with RMC-7977 + Palbociclib + FGK… ×2
KPC treated with RMC-7977 + Palbociclib + FGK… ×2
KPC treated with RMC-7977 + Palbociclib + FGK… ×2
How we read this: Read from 30 sample titles: 27 distinct titles with little repetition. 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
- GSM8882703 KPC treated with Vehicle for 7 days, Batch 2493, sorted, tumor compartment
- GSM8882704 KPC treated with Vehicle for 7 days, Batch 2493, sorted, CD45 compartment
- GSM8882705 KPC treated with Palbociclib for 7 days, Batch 2493, sorted, tumor compartment
- GSM8882706 KPC treated with Palbociclib for 7 days, Batch 2493, sorted, CD45 compartment
- GSM8882707 KPC treated with RMC-7977 for 7 days, Batch 2493, sorted, tumor compartment
- GSM8882708 KPC treated with RMC-7977 for 7 days, Batch 2493, sorted, CD45 compartment
- GSM8882709 KPC treated with RMC-7977 + Palbociclib for 7 days, Batch 2493, sorted, tumor compartment
- GSM8882710 KPC treated with RMC-7977 + Palbociclib for 7 days, Batch 2493, sorted, CD45 compartment
- GSM8882711 KPC treated with Palbociclib for 7 days, Batch 2706, sorted, CD45 compartment
- GSM8882712 KPC treated with Palbociclib for 7 days, Batch 2706, sorted, tumor compartment
- GSM8882713 KPC treated with RMC-7977 for 7 days, Batch 2706, sorted, CD45 compartment
- GSM8882714 KPC treated with RMC-7977 for 7 days, Batch 2706, sorted, tumor compartment
- GSM8882715 KPC treated with RMC-7977 + Palbociclib for 7 days, Batch 2706, sorted, CD45 compartment
- GSM8882716 KPC treated with RMC-7977 + Palbociclib for 7 days, Batch 2706, sorted, tumor compartment
- GSM8882717 KPC treated with Vehicle for 7 days, Batch 2706, sorted, CD45 compartment
- GSM8882718 KPC treated with Vehicle for 7 days, Batch 2706, sorted, tumor compartment
- GSM8882719 KPC treated with Palbociclib for 14 days, Batch 2718, sorted, CD45 compartment
- GSM8882720 KPC treated with Palbociclib for 14 days, Batch 2718, sorted, tumor compartment
- GSM8882721 KPC treated with RMC-7977 for 14 days, Batch 2718, sorted, CD45 compartment
- GSM8882722 KPC treated with RMC-7977 for 14 days, Batch 2718, sorted, tumor compartment
- GSM8882723 KPC treated with RMC-7977 + Palbociclib for 14 days, Batch 2718, sorted, CD45 compartment
- GSM8882724 KPC treated with RMC-7977 + Palbociclib for 14 days, Batch 2718, sorted, tumor compartment
- GSM8882725 KPC treated with Vehicle for 14 days, Batch 2718, sorted, CD45 compartment
- GSM8882726 KPC treated with Vehicle for 14 days, Batch 2718, sorted, tumor compartment
- GSM8882727 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 7 days, Batch 3036, sorted, CD45 compartment, Replicate 1
- GSM8882728 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 7 days, Batch 3036, sorted, CD45 compartment, Replicate 2
- GSM8882729 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 7 days, Batch 3413, unsorted, Replicate 1
- GSM8882730 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 7 days, Batch 3413, unsorted, Replicate 3
- GSM8882731 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 14 days, Batch 3431, unsorted, Replicate 1
- GSM8882732 KPC treated with RMC-7977 + Palbociclib + FGK4.5 for 14 days, Batch 3431, unsorted, Replicate 3
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- GSE236129 Activation of RAS/MEK/ERK signaling drives biliary differentiation in primary liver cancer [112UE] 80 samples shares ras
- GSE311286 Analysis of murine normal pancreatic organoids, pancreatitis-derived organoids, and PDAC organoids in complete media and of pancreatitis-derived organoids, and PDAC organoids cultured alone or cocultured with pancreatic stellate cells in reduced media 75 samples shares pdac
- GSE301303 Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivo 65 samples shares ras
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