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RNA-seq of AsPC-1 cell line-derived xenograft mouse tumors treated with a MEK-RAF molecular glue, IK-595

GSE277629 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2025/09/24 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 24 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
Homo sapiens (human)
Samples
24 samples: 6 conditions, mostly with about 4 replicates eachGroups 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.
Summary (written by the submitters)
MAPK pathway alterations are the most common oncogenic drivers. Among the approved therapies targeting this pathway are MEK and RAF inhibitors. However, therapeutic resistance and toxicities have limited their clinical success. To overcome these liabilities, we developed IK595, a potent MEK-RAF molecular glue. IK-595 traps MEK in an inactive complex with all RAF isoforms.
Read the full summary ↓
In addition, IK-595 precludes CRAF-mediated MEK reactivation and ARAF heterodimerization allowing for prolonged target engagement and durable MAPK pathway inhibition. This project aimed to explore gene expression modulation by IK-595 in AsPC-1 cell line-derived xenograft mice at different time points following last dose. Tumor RNA-seq was performed in AsPC-1 tumor-bearing mice treated with three doses of vehicle or IK-595 (at 6 mg/kg QOD). Tumors from the drug-treated mice were collected and profiled at the following time points after the last dose: 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours (four animals per time point group) - to understand longitudinal gene expression changes after dosing. A significant reduction in most ERK1/2 target genes was observed as early as 2 hours after the last dose, with maximal inhibition observed at 8 hours. Partial recovery of ERK1/2 target gene expression occurred at 24 hours, with most genes returning to baseline levels by 48 hours. While elevated pathway activation following chronic treatment of MAPK pathway inhibitors is known to be associated with resistance in the literature, the expression of ERK1/2 target genes in our study never rebounded above baseline levels upon IK-595 treatment.
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 GSE277629_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 PRJNA1162166 and SRA study SRP533252. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 4 replicates each
AsPC1 CDX tumor, vehicle-treated, 2 hours aft… ×4 AsPC1 CDX tumor, IK-595-treated, 2 hours afte… ×4 AsPC1 CDX tumor, IK-595-treated, 4 hours afte… ×4 AsPC1 CDX tumor, IK-595-treated, 8 hours afte… ×4 AsPC1 CDX tumor, IK-595-treated, 24 hours aft… ×4 AsPC1 CDX tumor, IK-595-treated, 48 hours aft… ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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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