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CDK4/6 and SHP2 mediate BRAF/MEK inhibitor resistance in Class 2 and 3 BRAF mutant cancers

GSE308451 Homo sapiens (human) RNA-seq (gene expression) 90 samples Submitted 2025/11/11 Platform 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)
Samples
90 samples: 45 conditions, mostly in duplicateGroups 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
Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trialNature communications · 2026
Summary (written by the submitters)
Class 2 and 3 non-V600E BRAF mutations are oncogenic drivers in many cancer types. Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600E BRAF mutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600E BRAF mutations.
Read the full summary ↓
The best objective response rate was 14% (3/21). By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and Class 2 & 3 BRAF mutant cell lines, we discovered MAPK-dependent and independent mechanisms of resistance to BRAF/MEK inhibition. These mechanisms included the acquisition of new mutations in NRAS, MAP2K1, RAF1, and RB in ctDNA at the time of disease progression. CDK4/6 and SHP2 were identified as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors were more effective than BRAF/MEK inhibitors alone in these cancers. https://doi.org/10.1038/s41467-025-68076-7
Published in
Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial
Rose AAN, Maxwell J, Rousselle E et al. · Nature communications 2026 · PMID 41484121 · doi:10.1038/s41467-025-68076-7
This dataset
Open GSE308451 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 GSE308451_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 PRJNA1330616 and SRA study SRP623357. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41484121) ↗
Study design
45 conditions, mostly in duplicate
MDA-MB-231 Parental 24h DMSO ×2 MDA-MB-231 Parental 24h Bini+Enco ×2 MDA-MB-231 Resistant 24h DMSO ×2 MDA-MB-231 Resistant 24h Bini+Enco ×2 HMV-II Parental 24h DMSO ×2 HMV-II Parental 24h Bini+Enco ×2 HMV-II Resistant 24h DMSO ×2 HMV-II Resistant 24h Bini+Enco ×2 +37 more

Supports a between-group comparison across 90 samples.

How we read this: 45 replicated groups read from 90 sample titles; they account for 90 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

+ 50 more — browse all 90 samples with per-sample file links →

Datasets on a similar topic

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