GEO series

Differential responses to selective CDK2 inhibitor BLU-222 is conditioned by tumor suppressors

GSE281746 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/12/22 Platform GPL11154

At a glance

RNA-seq (gene expression) · human · 18 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: 18 samples: 6 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: Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222Cancer research · 2025

Summary (written by the submitters)

The selective CDK2 inhibitor BLU-222 was evaluated for mechanisms of response in the context of ovarian and breast cancer models. Using sensors of cellular CDK activity, it was found that sensitivity to either CDK4/6 or CDK2 inhibition is related to the differential dependence on a single CDK for G1/S transition. Unlike CDK4/6 inhibitors, BLU-222 was able to robustly inhibit proliferation through cell cycle inhibition in both G1 and G2 phases.

Read the full summary ↓

However, it remained possible for cells to re-enter the cell cycle upon drug withdrawal. The anti-proliferative strength and impact on G1/S versus G2/M accumulation was found to be mediated by the RB tumor suppressor, as determined by functional perturbation strategies. To broaden the sensitivity to CDK2 inhibition, combinatorial drug screens were performed that identified both synergistic (e.g., CDK4/6 inhibitors) and antagonistic (e.g., WEE1 inhibitors) relationships. Models that were exceptionally sensitive to CDK2 inhibition displayed coordinate expression of Cyclin E1 and P16INK4A, an endogenous CDK4/6 inhibitor. Functional studies demonstrated that P16INK4A and CDK4/6 activity were key mediators of sensitivity to BLU-222. Clinical gene and protein expression analysis revealed a positive correlation between Cyclin E1 and P16INK4A and that ~25% of ovarian cancers exhibited coordinate expression of Cyclin E, P16INK4A, and RB, indicative of strong sensitivity to CDK2 inhibition. Together, this work advances a precision strategy for the use of CDK2 inhibitors in the context of ovarian and breast cancers.

Published in

Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222

Dommer AP, Kumarasamy V, Wang J et al. · Cancer research 2025 · PMID 39945638 · doi:10.1158/0008-5472.CAN-24-2244

This dataset

Open GSE281746 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 GSE281746_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 PRJNA1185646 and SRA study SRP544929. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39945638) ↗

Study design

6 conditions, mostly in triplicate

Kuramochi, DMSO, ×3 Kuramochi, BLU 125 nM, ×3 MDA-MB-157, DMSO, ×3 MDA-MB-157, BLU 100 nM, ×3 OVCAR-8, DMSO, ×3 OVCAR-8, BLU 250 nM, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

GSM8627466 Kuramochi, DMSO, rep 1 Kuramochi, DMSO,
GSM8627467 Kuramochi, DMSO, rep 2 Kuramochi, DMSO,
GSM8627468 Kuramochi, DMSO, rep 3 Kuramochi, DMSO,
GSM8627469 Kuramochi, BLU 125 nM, rep1 Kuramochi, BLU 125 nM,
GSM8627470 Kuramochi, BLU 125 nM, rep2 Kuramochi, BLU 125 nM,
GSM8627471 Kuramochi, BLU 125 nM, rep3 Kuramochi, BLU 125 nM,
GSM8627472 MDA-MB-157, DMSO, rep 1 MDA-MB-157, DMSO,
GSM8627473 MDA-MB-157, DMSO, rep 2 MDA-MB-157, DMSO,
GSM8627474 MDA-MB-157, DMSO, rep 3 MDA-MB-157, DMSO,
GSM8627475 MDA-MB-157, BLU 100 nM, rep 1 MDA-MB-157, BLU 100 nM,
GSM8627476 MDA-MB-157, BLU 100 nM, rep 2 MDA-MB-157, BLU 100 nM,
GSM8627477 MDA-MB-157, BLU 100 nM, rep 3 MDA-MB-157, BLU 100 nM,
GSM8627478 OVCAR-8, DMSO, rep 1 OVCAR-8, DMSO,
GSM8627479 OVCAR-8, DMSO, rep 2 OVCAR-8, DMSO,
GSM8627480 OVCAR-8, DMSO, rep 3 OVCAR-8, DMSO,
GSM8627481 OVCAR-8, BLU 250 nM, rep1 OVCAR-8, BLU 250 nM,
GSM8627482 OVCAR-8, BLU 250 nM, rep2 OVCAR-8, BLU 250 nM,
GSM8627483 OVCAR-8, BLU 250 nM, rep3 OVCAR-8, BLU 250 nM,

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