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BRD8 is a therapeutic vulnerability for overcoming resistance to dual ER/HER2 blockade therapy in HR+/HER2+ breast cancer [bulkRNA-seq]

GSE230326 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2026/03/20 Platform GPL20301
At a glance

Single-cell RNA-seq · human · 12 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
Homo sapiens (human)
Samples
12 samples: 3 × BT474_DMSO vs 3 × BT474_KO_DMSO vs 3 × BT474_Ner vs 3 × BT474_KO_NerGroups 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
Integrated Multiomic Profiling Identifies BRD8/EP400 as a Pivotal Chromatin Module Mediating Anti-HER2 Response in HR+/HER2+ Breast CancerCancer research · 2026
Summary (written by the submitters)
Hormone receptor (HR)-positive, HER2-positive breast cancers are resistant to endocrine and anti-HER2 therapies due to crosstalk between estrogen receptor (ER) and HER2. However, how anti-HER2 agents activate ER as a mechanism of resistance remains unknown. Using single-cell RNA sequencing, we identified Bromodomain Containing Protein 8 (BRD8) as a major mediator of ER activation in response to neratinib, a HER2 tyrosine kinase inhibitor.
Read the full summary ↓
BRD8 expression was rapidly induced by various anti-HER2 agents (neratinib, lapatinib and trastuzumab) and its expression positively correlates with ER. BRD8 regulates both ER-dependent and -independent growth promoting pathways. Moreover, BRD8 ablation re-sensitizes fulvestrant- or neratinib-resistant HR+/HER2+ cells to neratinib, suggesting that combinatorial targeting of BRD8 and HER2 attenuates signal crosstalk and possibly overcomes treatment resistance to dual anti-ER/HER2 blockade therapy. This work identifies BRD8 as not only a central hub for ER signaling activation upon anti-HER2 treatment, but also a druggable vulnerability for treating HR+/HER2+ breast cancer.
Published in
Integrated Multiomic Profiling Identifies BRD8/EP400 as a Pivotal Chromatin Module Mediating Anti-HER2 Response in HR+/HER2+ Breast Cancer
Gao A, Khatri PH, Ma G et al. · Cancer research 2026 · PMID 41886605 · doi:10.1158/0008-5472.CAN-25-4701
This dataset
Open GSE230326 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 GSE230326_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 PRJNA958245 and SRA study SRP433813. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41886605) ↗
Study design
3 × BT474_DMSO vs 3 × BT474_KO_DMSO vs 3 × BT474_Ner vs 3 × BT474_KO_Ner

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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