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BLU-222, a Potent CDK2 Inhibitor, Synergizes with CDK4/6 Inhibitors to Overcome Drug Resistance in HR–Positive and Triple-Negative Breast Cancer by Inducing p21 and p27

GSE282705 Homo sapiens (human) RNA-seq (gene expression) 90 samples Submitted 2025/11/18 Platform GPL24676Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 90 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
90 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
CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 inductionNature communications · 2026
Summary (written by the submitters)
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2−negative (HR+/HER2−) metastatic breast cancer, but resistance develops over time. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i is unclear. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2− and TNBC models, leading to increased apoptosis and cell cycle arrest.
Read the full summary ↓
In vivo, combining BLU-222 with palbociclib or ribociclib showed significant antitumor effects across 8 models, resulting in durable tumor regression and extended survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated p21 and p27 expression and enhanced p21 binding to CDK2 as well as p21 and p27 binding to CDK4 complexes. CRISPR knockout of p21 or p27 in palbociclib-resistant cells eliminated this synergy. Further, RNA sequencing showed that the combination treatment upregulated senescence and interferon pathways, offering insights into the observed therapeutic synergy.
Published in
CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction
Luo L, Wang Y, Bui T et al. · Nature communications 2026 · PMID 41571637 · doi:10.1038/s41467-025-67865-4
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 GSE282705_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 PRJNA1189832 and SRA study SRP547174. Searching any of these in the dataset finder brings you back here.

Samples in this study

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