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dc.contributor.authorVaclova, T
dc.contributor.authorGrazini, U
dc.contributor.authorWard, L
dc.contributor.authorO'Neill, D
dc.contributor.authorMarkovets, A
dc.contributor.authorHuang, X
dc.contributor.authorChmielecki, J
dc.contributor.authorHartmaier, R
dc.contributor.authorThress, KS
dc.contributor.authorSmith, PD
dc.contributor.authorBarrett, JC
dc.contributor.authorDownward, J
dc.contributor.authorde Bruin, EC
dc.date.accessioned2021-03-31T10:01:56Z
dc.date.available2021-03-31T10:01:56Z
dc.date.issued2021-03-19
dc.identifier.citationNature communications, 2021, 12 (1), pp. 1780 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4472
dc.identifier.eissn2041-1723
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-021-22057-8
dc.identifier.doi10.1038/s41467-021-22057-8en_US
dc.description.abstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M-positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.
dc.formatElectronic
dc.format.extent1780 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleClinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers.
dc.typeJournal Article
dcterms.dateAccepted2021-02-23
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-22057-8
rioxxterms.licenseref.startdate2021-03-19
rioxxterms.licenseref.startdate2021-03-19en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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 Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
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 Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.publication-statusPublished
pubs.volume12en_US
pubs.embargo.termsNot known
icr.researchteamLung Cancer Group
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/