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A novel combination of CDK4/6 and PI3K inhibitors exhibits highly synergistic activity and translational potential in Ewing sarcoma.

GSE279738 Homo sapiens (human) RNA-seq (gene expression) 32 samples Submitted 2026/05/31 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 32 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
32 samples: 12 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.
Summary (written by the submitters)
Ewing sarcoma is a highly aggressive solid tumor malignancy and the second most common bone cancer in children. Ewing sarcoma is driven primarily by EWS-FLI, a fusion oncoprotein that has been notoriously difficult to target with traditional pharmacological agents. Compared to adult cancers, pediatric malignancies are rarely driven by readily druggable oncogenic targets and there are few incentives for developing drugs for challenging targets restricted to relatively uncommon cancer types.
Read the full summary ↓
In addition, the effectiveness of single-agent therapies for cancer treatment is often limited. Furthermore, there are numerous examples of promising combinations of preclinical small molecules that are never tested in pediatric clinical trials because agents fail to reach the market due to limited efficacy for common adult cancers. Therefore, the identification of novel effective candidate treatment combinations comprised of anti-cancer drugs already commercially available would likely expedite the development of clinical trials for patients with pediatric cancers. To identify candidate treatment combinations for Ewing sarcoma, we performed a high-throughput drug screening with 180 combinations of tyrosine kinase inhibitors, cell cycle inhibitors, and chemotherapies, that were largely FDA approved or in late stages of clinical development. The results of the screen revealed that a CDK4/6 inhibitor ribociclib combined with a PI3K inhibitor copanlisib exhibited strong synergistic anti-Ewing sarcoma activity. We showed that this combination induced apoptosis and cell cycle arrest more effectively than either agent alone in vitro and impaired tumor proliferation and prolonged survival in vivo compared to mice treated with vehicle or single-agent therapy. Our findings identified a new candidate therapeutic option for Ewing sarcoma patients using FDA-approved drugs and provide a resource of additional potential synergistic combinations for future validation.
This dataset
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.

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 GSE279738_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1174183 and SRA study SRP539205. Searching any of these in the dataset finder brings you back here.

Study design
12 conditions, mostly in triplicate
EW8, DMSO, ×3 EW8, Ribociclib, ×3 EW8, Copanlisib, ×3 EW8, Combination, ×3 TC32, DMSO, ×3 TC32, Ribociclib, ×3 TC32, Copanlisib, ×3 TC32, Combination, ×3 +4 more

Supports a between-group comparison across 32 samples.

How we read this: 12 replicated groups read from 32 sample titles; they account for 32 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.