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ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC [Degrader RNA-seq]

GSE298925 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2025/07/15 Platform GPL34295
At a glance

RNA-seq (gene expression) · human · 48 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
48 samples: 16 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
ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDACNature chemical biology · 2026
Summary (written by the submitters)
Over 95% of pancreatic ductal adenocarcinomas (PDAC) harbor oncogenic mutations in K-Ras. However, upon treatment with K-Ras inhibitors, PDAC cancer cells undergo rapid metabolic reprogramming towards an oxidative phosphorylation-dependent, drug-resistant state. In this work, we demonstrate that this metabolic shift is associated with upregulation of the transcription factor ZBTB11, and both the metabolic state and the K-Ras inhibitor drug resistance can be attenuated by ZBTB11 depletion.
Read the full summary ↓
We develop molecular glue degraders of ZBTB11 and demonstrate that they reprogram the aberrant transcriptome, proteome, metabolome, and bioenergetics of K-Ras inhibitor resistant PDAC, resensitizing them to K-Ras inhibition. ZBTB11 degradation leverages cell-type and cell-state specific differences in gene regulatory mechanisms controlling OXPHOS-pathway transcripts to selectively target the K-Ras inhibitor resistant state in PDAC while sparing hiPSC-derived neurons. Together, this work establishes ZBTB11 as a druggable vulnerability in K-Ras inhibitor-resistant PDAC and provides a suite of molecular glue degrader tool compounds to investigate its function.
Published in
ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC
Tran NL, Jiang J, Ma M et al. · Nature chemical biology 2026 · PMID 40789946 · doi:10.1038/s41589-025-01978-1
This dataset
Open GSE298925 in finder → Find more human 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 GSE298925_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 PRJNA1271833 and SRA study SRP589789. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40789946) ↗
Study design
16 conditions, mostly in triplicate
JWJ-01-306, 5 hr, ×3 JWJ-01-306+Sotorasib, 5 hr, ×3 DMSO, 5 hr, ×3 Sotorasib, 5 hr, ×3 JWJ-01-306, 1 day, ×3 JWJ-01-306+Sotorasib, 1 day, ×3 DMSO, 1 day, ×3 Sotorasib, 1 day, ×3 +8 more

Supports a between-group comparison across 48 samples.

How we read this: 16 replicated groups read from 48 sample titles; they account for 48 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

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