← BioTransfer GEO Dataset Finder
GEO series

Mechanisms of response and tolerance to active RAS inhibition in KRAS-mutant NSCLC

GSE270541 Mus musculus (mouse) Single-cell RNA-seq 35 samples Submitted 2024/06/27 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 35 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
35 samples: 8 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.
Paper
Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant Non-Small Cell Lung CancerCancer discovery · 2024
Summary (written by the submitters)
Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the anti-tumor activity of the RAS(ON) multi-selective tri-complex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in KRASG12C-mutant NSCLC.
Read the full summary ↓
Broad-spectrum, reversible RASGTP inhibition with or without concurrent covalent targeting of active RASG12C yielded superior and differentiated antitumor activity across diverse co-mutational KRASG12C-mutant NSCLC mouse models of primary or acquired RASG12C(ON) or (OFF) inhibitor resistance. Interrogation of time-resolved single cell transcriptional responses established an in vivo atlas of multi-modal acute and chronic RAS pathway inhibition in the NSCLC ecosystem and uncovered a regenerative mucinous transcriptional program that supports long-term tumor cell persistence. In patients with advanced KRASG12C-mutant NSCLC, the presence of mucinous histological features portended poor response to sotorasib or adagrasib. Our results have potential implications for personalized medicine and the development of rational RAS inhibitor-anchored therapeutic strategies.
Published in
Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant Non-Small Cell Lung Cancer
Araujo HA, Pechuan-Jorge X, Zhou T et al. · Cancer discovery 2024 · PMID 38975897 · doi:10.1158/2159-8290.CD-24-0421
This dataset
Open GSE270541 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 GSE270541_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1127471 and SRA study SRP515646. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38975897) ↗
Study design
8 conditions, mostly with about 4 replicates each
KL2A drug released, rechallenged with RM-042, ×8 KL2 treated with Vehicle for 7 days, ×4 KL2 treated with Sotorasib for 7 days, ×4 KL2 treated with RM-029 for 7 days, ×4 KL2 treated with Combo RM-029 + RM-4550 for 7… ×4 KL2 treated with RM-042 for 7 days, ×4 KL2 treated with Combo RM-029 + RM-042 for 7 … ×4 KL2A drug released, rechallenged with Vehicle, ×3

Supports a case/control comparison: 20 samples read as cases, 3 as controls.

How we read this: 8 replicated groups read from 35 sample titles; they account for 35 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

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.