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Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas.

GSE298261 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2025/07/29 Platform GPL34281
At a glance

RNA-seq (gene expression) · human · 20 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
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
20 samples: 10 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
Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomasCommunications biology · 2025
Summary (written by the submitters)
Broad-spectrum multi-target tyrosine kinase inhibitors (mTKIs) are clinically approved for the treatment of soft tissue sarcomas (STS). However, acquired resistance inevitably arises in the majority of STS patients. There is therefore an urgent need to identify new strategies to overcome resistance and achieve durable treatment responses.
Read the full summary ↓
Here we show that STS cells that acquire resistance to clinically relevant mTKIs are cross-resistant to one another and sequential treatment does not delay the acquisition of drug resistance. Instead, we find that en route to acquiring drug resistance, STS cells develop collateral sensitivities to alternative drugs. We demonstrate that the mTKI sitravatinib rapidly induces collateral sensitivity to the FGFR inhibitor infigratinib which can be exploited for adaptive therapy to suppress STS cell growth. This study provides proof-of-principle that collateral sensitivity may be an effective strategy for overcoming resistance to mTKIs and this novel approach should be explored in the design of future trials.
Published in
Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas
Elms ML, Jenks AD, Chowdhury A et al. · Communications biology 2025 · PMID 40781553 · doi:10.1038/s42003-025-08652-1
This dataset
Open GSE298261 in finder → Find more human RNA-seq datasets → Soft tissue sarcoma landscape →
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 GSE298261_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 PRJNA1268584 and SRA study SRP588011. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40781553) ↗
Study design
10 conditions, mostly in duplicate
A204, parental, ×2 A204, pazopanib resistant, ×2 A204, regorafenib resistant, ×2 A204, sitravatinib resistant, ×2 A204, anlotinib resistant, ×2 G402, parental, ×2 G402, pazopanib resistant, ×2 G402, regorafenib resistant, ×2 +2 more

Supports a between-group comparison across 20 samples.

How we read this: 10 replicated groups read from 20 sample titles; they account for 20 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
More Soft tissue sarcoma datasets

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