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The CDK4/6 inhibitor dalpiciclib augments the antitumor efficacy of enzalutamide in preclinical models of castration-resistant prostate cancer through inhibition of MCM4-mediated DNA replication

GSE325471 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/08/19 Platform GPL29480
At a glance

RNA-seq (gene expression) · human · 12 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
Prostate cancerThis series is part of our curated briefing on it.
Samples
12 samples: 3 × DMSO vs 3 × DAL vs 3 × ENZ vs 3 × DAL_ENZGroups 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)
Castration-resistant prostate cancer (CRPC) is a lethal malignancy characterized by frequent alterations in cell cycle regulatory pathways, particularly the Cyclin/CDK/RB axis. Several clinical trials are currently evaluating CDK4/6 inhibitors in prostate cancer; however, clinical evidence remains limited.Although the androgen receptor (AR) inhibitor enzalutamide (ENZ) initially shows therapeutic efficacy, patients eventually develop resistance, and monotherapy provides limited antitumor benefit.
Read the full summary ↓
In this study, we performed pharmacological profiling, genomic dependency analysis, RNA sequencing, and functional validation across multiple in vitro and in vivo preclinical CRPC models. The combination of ENZ and the CDK4/6 inhibitor dalpiciclib (DAL) exhibited potent antitumor activity in CRPC cell lines and a cell-derived xenograft (CDX) model. Furthermore, ENZ combined with DAL suppressed cell cycle progression, migration, and DNA replication while promoting apoptosis in CRPC cells. Mechanistically, ENZ inhibited AR-mediated transcriptional activation of MCM4, a key DNA helicase component, thereby enhancing the inhibitory effect of CDK4/6 blockade on DNA replication and resulting in a marked synergistic antitumor response. Collectively, these findings propose the ENZ-DAL combination as a promising therapeutic strategy to improve treatment efficacy and support further clinical evaluation of this regimen in patients with CRPC.
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 GSE325471_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 PRJNA1440244 and SRA study SRP685356. Searching any of these in the dataset finder brings you back here.

Study design
3 × DMSO vs 3 × DAL vs 3 × ENZ vs 3 × DAL_ENZ

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
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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.