GEO series

Imlunestrant: A next-generation oral SERD overcomes ESR1 mutant resistance in estrogen receptor-positive breast cancer

GSE295024 Homo sapiens (human) RNA-seq (gene expression) 72 samples Submitted 2025/04/18 Platform GPL34281

At a glance

RNA-seq (gene expression) · human · 72 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: Breast cancerThis series is part of our curated briefing on it.
Samples: 72 samples
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: Imlunestrant a next-generation oral SERD overcomes ESR1 mutant resistance in estrogen receptor-positive breast cancerJCI insight · 2025

Summary (written by the submitters)

Estrogen receptor alpha (ER) is a critical driver of tumorigenesis and tumor progression in most breast cancers. Endocrine therapies targeting the ER are the cornerstone treatments in hormone receptor-positive breast cancer. Resistance to these therapies poses a significant clinical challenge and is due to diverse mechanisms. Some of these mechanisms, particularly through estrogen independent activity and the ESR1 mutations, remain dependent on the estrogen axis providing a rationale for the development of next-generation endocrine therapies.

Read the full summary ↓

This study investigates the preclinical efficacy of imlunestrant, a next-generation oral selective estrogen receptor degrader, in ER-positive breast cancer pre-clinical models, including models harboring the Y537S ESR1 mutation, a prevalent and potent ER activating mutation. Imlunetsrant demonstrated pure antagonistic activity and effective degradation of both wild-type and mutant ER, significantly suppressing cell growth. In vivo, imlunestrant outperformed fulvestrant leading to tumor regression in a patient derived xenograft harboring the Y537S ESR1 mutation. Cyclic multiplexed immunofluorescence and transcriptomic analysis revealed enhanced cell cycle arrest and downregulation of estrogen-responsive genes with imlunestrant treatment. Additionally, a genome wide CRISPR knock-out screen identified several vulnerabilities that were either persistent or gained after imlunestrant treatment, which provides a rational for future studies of combination treatments with imlunestrant. In summary, these results highlight the on target and selective potent activity of imlunestrant, which can circumvent resistance engendered by the Y537S ESR1 mutation and support the clinical development of imlunestrant.

Published in

Imlunestrant a next-generation oral SERD overcomes ESR1 mutant resistance in estrogen receptor-positive breast cancer

Sherman S, Sandusky ZM, Russo D et al. · JCI insight 2025 · PMID 40327396 · doi:10.1172/jci.insight.188051

This dataset

Open GSE295024 in finder → Find more human RNA-seq datasets → Breast 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 GSE295024_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 PRJNA1252653 and SRA study SRP579649. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40327396) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 72 more — browse all 72 samples with per-sample file links →

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Search all human RNA-seq datasets in GEO →

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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.