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Combined therapy with DR5- targeting antibody-drug conjugate and CDK inhibitors as a novel strategy for advanced MSS and MSI-H colorectal cancer

GSE289746 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/04/24 Platform GPL24676
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)
Samples
12 samples: 3 × P53R cells, Control, 2Day, vs 3 × P56R cells, Oba01, 2Day, vs 3 × P56R cells, Abemaciclib, 2Day, vs 3 × P56R cells, Combination, 2Day,Groups 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
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancerCell reports. Medicine · 2025
Summary (written by the submitters)
Targeted therapies for advanced microsatellite stable (MSS) subtypes of colorectal cancer (CRC) continue to present significant clinical challenges. Death receptor 5 (DR5/TRAIL-R2) is an apoptotic receptor frequently overexpressed in various cancers. Evidence suggests that DR5-targeting antibody drug conjugates (ADC) show promising efficacy in several cancers.
Read the full summary ↓
In this study, we demonstrated DR5 as a clinically significant target for CRC by analyzing tissue microarrays from advanced CRC cohorts (473 MSS cases and 36 MSI-H cases), as well as data from a TCGA cohort comprising 418 cases. Our novel clinical-stage DR5-targeting ADC, Oba01, designed to deliver the microtubule-disrupting agent MMAE, shows superior therapeutic efficacy across various CRC cell lines, patient-derived xenografts (PDXs), and corresponding organoids (PDXOs), regardless of their MSS or MSI-H status. Importantly, our functional RNAseq and proteomic analysis of the impact of Oba01 on global gene expression revealed that the cell cycle pathway and cyclin-dependent kinases (CDKs) are mechanistically synergistic targets of the drug's effects. Supporting this idea, we presented solid evidence to show Oba01 and abemaciclib, a FDA-approved CDK4/6 inhibitor for metastatic breast cancer, substantially synergize across various clinically relevant models derived from advanced CRC patients with both MSS and MSI-H status, in both in vitro and in vivo settings. The fact that this synergy spans multiple CDK inhibitors further highlights the potential of combining DR5-mediated delivery of MMAE with CDK inhibition as a novel therapeutic strategy for advanced CRC patients, especially those with the challenging to treat MSS subtype.
Published in
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer
Zhou D, Tang E, Wang W et al. · Cell reports. Medicine 2025 · PMID 40449480 · doi:10.1016/j.xcrm.2025.102158
This dataset
Open GSE289746 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 GSE289746_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 PRJNA1224440 and SRA study SRP564231. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40449480) ↗
Study design
3 × P53R cells, Control, 2Day, vs 3 × P56R cells, Oba01, 2Day, vs 3 × P56R cells, Abemaciclib, 2Day, vs 3 × P56R cells, Combination, 2Day,

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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