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Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib

GSE252245 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2024/12/31 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
Lower-grade gliomaThis 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
Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclibiScience · 2025
Summary (written by the submitters)
Isocitrate dehydrogenase (IDH)-mutant gliomas have distinctive metabolic and biological traits that may render them susceptible to targeted treatments. Here, by conducting a high-throughput drug screen, we pinpointed a specific susceptibility of IDH-mutant gliomas to zotiraciclib (ZTR). ZTR exhibited selective growth inhibition across multiple IDH-mutant glioma in vitro and in vivo models.
Read the full summary ↓
Mechanistically, ZTR at low doses suppressed CDK9 and RNA Pol II phosphorylation in IDH-mutant cells, disrupting mitochondrial function and NAD+ production, causing oxidative stress.,. Integrated biochemical profiling of ZTR kinase targets and transcriptomics unveiled that ZTR-induced bioenergetic failure was linked to the suppression of PIM kinase activity. We posit that the combination of mitochondrial dysfunction and an inability to adapt to oxidative stress resulted in significant cell death upon ZTR treatment, ultimately increasing the therapeutic vulnerability of IDH-mutant gliomas. These findings prompted a clinical trial evaluating ZTR in IDH-mutant gliomas towards precision medicine (NCT05588141).
Published in
Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib
Pang Y, Li Q, Sergi Z et al. · iScience 2025 · PMID 40241769 · doi:10.1016/j.isci.2025.112283
This dataset
Open GSE252245 in finder → Find more human RNA-seq datasets → Lower-grade glioma 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 GSE252245_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 PRJNA1059002 and SRA study SRP480634. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40241769) ↗
Study design
8 conditions, mostly in triplicate
GSC923 cells, Control, 24 hours, ×3 GSC923 cells, Treated, 24 hours, ×3 TS603 cells, Control, 24 hours, ×3 TS603 cells, Treated, 24 hours, ×3 GSC923 cells, Control, 48 hours, ×3 GSC923 cells, Treated, 48 hours, ×3 TS603 cells, Control, 48 hours, ×3 TS603 cells, Treated, 48 hours, ×3

Supports a case/control comparison: 12 samples read as cases, 12 as controls.

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 Lower-grade glioma datasets

Search all human RNA-seq datasets in GEO →

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