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Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition

GSE332586 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2026/05/21 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 36 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
Ewing sarcomaThis series is part of our curated briefing on it.
Samples
36 samples: 11 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
Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibitionMolecular therapy. Oncology · 2026
Summary (written by the submitters)
Bone sarcomas are rare and aggressive pediatric cancers with limited progress in targeted therapy development, partly due to the poor physiological relevance of conventional two-dimensional (2D) culture systems used for preclinical testing. To address this gap, we developed a standardized three-dimensional (3D) culture and drug-testing platform for Ewing sarcoma (ES) and osteosarcoma (OS) that more accurately recapitulates in vivo tumor biology.
Read the full summary ↓
Notably, gene-expression analyses demonstrated that ES and OS spheroids transcriptionally converge toward patient tumor cell states, underscoring their physiological relevance for preclinical testing. Across 3D spheroids, bioprinted constructs, and patient-derived xenograft (PDX) cultures, we observed a consistent activation and dependency on the mevalonate pathway in ES. Leveraging this platform, we identified a selective therapeutic synergy between statins, which inhibit mevalonate pathway flux, and BCL-xL inhibitors—a vulnerability not detectable in 2D cultures. Importantly, this synergistic interaction was tumor-specific and absent in non-malignant fibroblasts, indicating a favorable therapeutic window. Together, these findings highlight the mevalonate pathway as a targetable metabolic dependency in ES and demonstrate how physiologically grounded 3D models can uncover clinically actionable treatment strategies that remain hidden in traditional 2D systems.
Published in
Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition
Radic-Sarikas B, Markovic M, Zylka MM et al. · Molecular therapy. Oncology 2026 · PMID 42281954 · doi:10.1016/j.omton.2026.201229
This dataset
Open GSE332586 in finder → Find more human RNA-seq datasets → Ewing sarcoma 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 GSE332586_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 PRJNA1468652 and SRA study SRP702386. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42281954) ↗
Study design
11 conditions, mostly in triplicate
sta-et-1 spheroids d7 ×3 sta-os-5 spheroids d4 ×3 sta-os-5 spheroids d7 ×3 os143b-gfp spheroids d4 ×3 os143b-gfp spheroids d7 ×3 os143b spheroids d4 ×3 os143b spheroids d7 ×3 sta-et-1 spheroids d4 ×2 +10 more

Supports a between-group comparison across 29 samples.

How we read this: 11 replicated groups read from 36 sample titles; they account for 29 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 Ewing sarcoma datasets

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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.