Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leveraging experimental evolution to extract predictive collateral drug response signatures in Ewings Sarcoma

ABSTRACT: Therapeutic options for patients with relapsed or refractory Ewings sarcoma (EWS) remain limited. Collateral sensitivity, where resistance to one drug confers sensitivity to another, could be leveraged to optimize chemotherapy for EWS. Gene expression signatures that predict collateral sensitivity states can be used to guide treatment selection in an evolution-informed manner. To generate such biomarkers, we experimentally evolved resistance to first-line EWS chemotherapy in independent replicates of an EWS cell line, all originating from the same ancestor population. Throughout, we measured collateral responses across a panel of anticancer drugs and quantified transcriptomic changes. Collateral drug responses varied across replicate evolutionary trajectories, but convergent states of collateral sensitivity emerged across different replicates at different times. By associating these convergent phenotypes with gene expression patterns, we derived a library of predictive signatures for numerous drugs. These signatures accurately distinguished states of collaterally sensitivity from states of collateral resistance within our dataset, irrespective of a replicate's evolutionary history. Our findings demonstrate that gene expression signatures can predict collateral sensitivity in EWS, providing a foundation for personalized therapeutic strategies. This approach also establishes a generalizable workflow for developing predictive biomarkers to guide chemotherapy selection in patients with rare diseases that lack reliable second-line chemotherapy regimens.

ORGANISM(S): Homo sapiens

PROVIDER: GSE325674 | GEO | 2026/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Collateral Responses to Classical Cytotoxic Chemotherapies are Heterogeneous and Sensitivities are Sparse

Project description:Chemotherapy resistance is a major obstacle to curing cancer patients. Combination drug regimens have shown promise as a method to overcome resistance; however, to date only some cancers have been cured with this method. Collateral sensitivity – the phenomenon whereby resistance to one drug is co-occurrent with sensitivity to a second drug – has been gaining traction as a promising new concept to guide rational design of combination regimens. Here we evolved over 100 subclones of the Eµ-Myc; p19ARF -/- cell line to be resistant to one of four classical chemotherapy agents: doxorubicin, vincristine, paclitaxel, and cisplatin. We then surveyed collateral responses to acquisition of resistance to these agents. Although numerous collateral sensitivities have been documented for antibiotics and targeted cancer therapies, we observed only one collateral sensitivity: half of cell lines that acquired resistance to paclitaxel also acquired a collateral sensitivity to verapamil. However, we found that the mechanism of this collateral sensitivity was unrelated to the mechanism of paclitaxel resistance. Interestingly, we observed heterogeneity in the phenotypic response to acquisition of resistance to most of the drugs we tested, most notably for paclitaxel, suggesting the existence of multiple different states of resistance. Surprisingly, this phenotypic heterogeneity in paclitaxel resistant cell lines was unrelated to transcriptomic heterogeneity among those cell lines. These features of phenotypic and transcriptomic heterogeneity must be taken into account in future studies of treated tumor subclones and in design of chemotherapy combinations.

2022-03-23 | GSE166425 | GEO

Transcription profiling of human Ewing sarcoma primary tumors of patients to determine molecular predictors of outcome.

Project description:The improvement of Ewing's sarcoma (EWS) therapy is currently linked to find strategies to select patients with poor and good prognosis at diagnosis and to generate modified treatment regimens. In this study, we analyze the molecular factors governing EWS response to chemotherapy in order to identify genetic signatures that may be used for risk-adapted therapy. Experiment Overall Design: Affimetrix platform was used for profiling 30 primary tumors of patients that were classified according to event-free survival and 7 metastasis. NED: no evidence of diseaase (event-free); REL: relapse; MET: metastasis. For selected genes, Real-Time PCR was applied in 42 EWS primary tumors as validation assay. MTT test was used to evaluate in vitro drug sensitivity.

2008-10-21 | E-GEOD-12102 | biostudies-arrayexpress

Escherichia coli

Project description:Collateral Sensitivity Associated with Antibiotic Resistance Plasmids

| PRJNA644278 | ENA

Mismanagement of Cellular Iron Leads to Ferroptosis Susceptibility in Cancer Cells Surviving Chemotherapy

Project description:Despite centuries of research, metastatic cancer remains incurable due to resistance against all conventional cancer therapeutics. Alternative strategies leveraging non-proliferative vulnerabilities in cancer are required to overcome cancer recurrence. Ferroptosis is an iron dependent cell death pathway that has shown promising pre-clinical activity in several contexts of therapeutic resistant cancer. However, ferroptosis sensitivity is highly variable across tissue types and cell state posing a challenge for clinical translation. We describe a convergent phenotype induced by chemotherapy where cells surviving chemotherapy have similar transcriptomic signatures and dysregulated iron homeostasis, regardless of initial cell type or chemotherapy used. Elevated labile iron levels are counteracted by NRF2 signaling that does not alleviate the amount of labile iron. Selectively inhibiting GPX4 leads to uniform susceptibility to ferroptosis in surviving cells, highlighting the common reliance on lipid peroxidation defenses. Cellular iron dysregulation is a vulnerability of chemoresistant cancer cells that can be leveraged by triggering ferroptosis

2025-05-13 | GSE283982 | GEO

Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants

Project description:Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants

| PRJNA641152 | ENA

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

Project description: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. 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.

2025-07-29 | GSE298261 | GEO

Project description:Identifying states of collateral sensitivity during the evolution of therapeutic resistance in Ewings sarcoma

| PRJNA630293 | ENA

Mutational Basis of Ceftazidime-Borrelidin A Collateral Sensitivity in Escherichia coli

Project description:Genomics of Collateral Sensitivity

| PRJEB94349 | ENA

Overcoming resistance to conventional drugs in Ewing’s sarcoma and identification of molecular predictors of outcome.

2008-07-15 | GSE12102 | GEO

Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections

Project description:Chronic Pseudomonas aeruginosa infections evades antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P.aeruginosa towards clinically relevant antibiotics leads to phenotypic convergence towards distinct states. These states are associated with collateral sensitivity towards several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In depth investigation of chronic P.aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.

2018-10-23 | PXD007972 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data