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dc.contributor.authorRomo-Morales, Aen_US
dc.contributor.authorAladowicz, Een_US
dc.contributor.authorBlagg, Jen_US
dc.contributor.authorGatz, SAen_US
dc.contributor.authorShipley, JMen_US
dc.date.accessioned2019-06-20T11:20:42Z
dc.date.issued2019-09
dc.identifier.citationPediatric blood & cancer, 2019, 66 (9), pp. e27888 - ?
dc.identifier.issn1545-5009
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3263
dc.identifier.eissn1545-5017
dc.identifier.doi10.1002/pbc.27888
dc.description.abstractBackground Ewing sarcoma and desmoplastic small round cell tumors (DSRCT) are rare and clinically aggressive sarcomas usually characterized by oncogenic fusion proteins involving EWS. Emerging studies of Ewing sarcoma have demonstrated EWS-FLI1-driven chromatin remodeling as a key aspect of tumorigenicity. In particular, the lysine-specific demethylase KDM1A/LSD1 is linked to transcriptional regulation of target genes orchestrated by the EWS portion of the fusion protein interacting with repressive chromatin-remodeling complexes. Consistent with this model, depletion of KDM1A supports it is a molecular therapeutic target in Ewing sarcoma cells, but effective drugs need to be identified. Procedure A comprehensive phenotypic analysis of the effects of catalytic KDM1A inhibitors ORY-1001 and GSK2879552, including clinically relevant doses, was carried out in 2D and 3D spheroid models of Ewing sarcoma and DSRCT. Results Catalytic inhibition of KDM1A did not affect cell viability in 2D and 3D assays and had no impact on invasion in a 3D assay. Conclusions Overall, evidence presented here does not support inhibition of KDM1A catalytic demethylase activity as an effective therapeutic strategy for Ewing sarcoma or DSRCT. However, roles of KDM1A beyond its demethylase activity should be considered for these sarcomas.
dc.formatPrint-Electronic
dc.format.extente27888 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectRNA-Binding Protein EWS
dc.subjectOncogene Proteins, Fusion
dc.subjectAntineoplastic Agents
dc.subjectEnzyme Inhibitors
dc.subjectProto-Oncogene Protein c-fli-1
dc.subjectHistone Demethylases
dc.subjectSarcoma, Ewing
dc.titleCatalytic inhibition of KDM1A in Ewing sarcoma is insufficient as a therapeutic strategy.
dc.typeJournal Article
dcterms.dateAccepted2019-05-31
rioxxterms.versionofrecord10.1002/pbc.27888
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPediatric blood & cancer
pubs.issue9
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume66
pubs.embargo.termsNot known
icr.researchteamSarcoma Molecular Pathologyen_US
dc.contributor.icrauthorRomo-Morales, Antonioen
dc.contributor.icrauthorShipley, Janeten
dc.contributor.icrauthorRomo Morales, Antonioen


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