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CDK12/13 inhibition in NSCLC cell lines with acquired resistance to sotorasib

GSE288707 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2025/10/07 Platform GPL30173
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)
Topic
Lung cancerThis series is part of our curated briefing on it.
Samples
24 samples: 8 conditions, mostly in triplicateGroups 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
Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C InhibitorsCancer research · 2026
Summary (written by the submitters)
The efficacy of KRAS-G12C inhibitors in lung cancer is limited by the rapid onset of acquired resistance. While divergent mechanisms of resistance across patients and preclinical models have complicated efforts to identify therapeutic strategies for sotorasib-resistant cancers, we found that sotorasib-resistant H358 and LU65 cell lines, which have distinct mechanisms of resistance and drug sensitivity profiles, both exhibited increased vulnerability to treatment with SR-4835, an inhibitor of the transcriptional kinases CDK12 and CDK13.
Read the full summary ↓
To identify CDK12/13-dependent genes linked to the increased sensitivity we observed in sotorasib-resistant over parental cells, we treated parental and sotorasib-resistant H358 and LU65 cells with SR-4835 and performed RNA sequencing.
Published in
Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C Inhibitors
Stern YE, Ghosh P, Peroza J et al. · Cancer research 2026 · PMID 41165466 · doi:10.1158/0008-5472.CAN-25-0450
This dataset
Open GSE288707 in finder → Find more human RNA-seq datasets → Lung cancer landscape →
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 GSE288707_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 PRJNA1219106 and SRA study SRP561458. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41165466) ↗
Study design
8 conditions, mostly in triplicate
Sotorasib-resistant H358, DMSO control, biol ×3 Sotorasib-resistant H358, SR-4835, biol ×3 Parental H358, DMSO control, biol ×3 Parental H358, SR-4835, biol ×3 Sotorasib-resistant LU65, DMSO control, biol ×3 Sotorasib-resistant LU65, SR-4835, biol ×3 Parental LU65, DMSO control, biol ×3 Parental LU65, SR-4835, biol ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 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
More Lung cancer datasets

Search all human RNA-seq datasets in GEO →

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