dc.contributor.author | Vaclova, T | |
dc.contributor.author | Grazini, U | |
dc.contributor.author | Ward, L | |
dc.contributor.author | O'Neill, D | |
dc.contributor.author | Markovets, A | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Chmielecki, J | |
dc.contributor.author | Hartmaier, R | |
dc.contributor.author | Thress, KS | |
dc.contributor.author | Smith, PD | |
dc.contributor.author | Barrett, JC | |
dc.contributor.author | Downward, J | |
dc.contributor.author | de Bruin, EC | |
dc.date.accessioned | 2021-03-31T10:01:56Z | |
dc.date.available | 2021-03-31T10:01:56Z | |
dc.date.issued | 2021-03-19 | |
dc.identifier.citation | Nature communications, 2021, 12 (1), pp. 1780 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4472 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-22057-8 | |
dc.description.abstract | Advanced 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.format | Electronic | |
dc.format.extent | 1780 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-02-23 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-22057-8 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-03-19 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Lung Cancer Group | |
icr.researchteam | Lung Cancer Group | |
dc.contributor.icrauthor | Downward, Julian David Harry | |