dc.contributor.author | Pancholi, S | |
dc.contributor.author | Simigdala, N | |
dc.contributor.author | Ribas, R | |
dc.contributor.author | Schuster, E | |
dc.contributor.author | Leal, MF | |
dc.contributor.author | Nikitorowicz-Buniak, J | |
dc.contributor.author | Rega, C | |
dc.contributor.author | Bihani, T | |
dc.contributor.author | Patel, H | |
dc.contributor.author | Johnston, SR | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Martin, L-A | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-02-21T13:33:53Z | |
dc.date.available | 2023-02-21T13:33:53Z | |
dc.date.issued | 2022-11-29 | |
dc.identifier | ARTN 125 | |
dc.identifier | 10.1038/s41523-022-00483-1 | |
dc.identifier.citation | npj Breast Cancer, 2022, 8 (1), pp. 125 - | |
dc.identifier.issn | 2374-4677 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5695 | |
dc.identifier.eissn | 2374-4677 | |
dc.identifier.eissn | 2374-4677 | |
dc.identifier.doi | 10.1038/s41523-022-00483-1 | |
dc.description.abstract | The selective oestrogen receptor (ER) degrader (SERD), fulvestrant, is limited in its use for the treatment of breast cancer (BC) by its poor oral bioavailability. Comparison of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, demonstrates both drugs impact tumour growth of ER+ patient-derived xenograft models harbouring several ESR1 mutations but that elacestrant is active after acquired resistance to fulvestrant. In cell line models of endocrine sensitive and resistant breast cancer both drugs impact the ER-cistrome, ER-interactome and transcription of oestrogen-regulated genes similarly, confirming the anti-oestrogenic activity of elacestrant. The addition of elacestrant to CDK4/6 inhibitors enhances the antiproliferative effect compared to monotherapy. Furthermore, elacestrant inhibits the growth of palbociclib-resistant cells. Lastly, resistance to elacestrant involves Type-I and Type-II receptor tyrosine kinases which are amenable to therapeutic targeting. Our data support the wider clinical testing of elacestrant. | |
dc.format | Electronic | |
dc.format.extent | 125 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | npj Breast Cancer | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Oncology | |
dc.subject | ESR1 MUTATIONS | |
dc.subject | ANTITUMOR-ACTIVITY | |
dc.subject | DEGRADER SERD | |
dc.subject | DOUBLE-BLIND | |
dc.subject | EXPRESSION | |
dc.subject | RAD1901 | |
dc.subject | FOXA1 | |
dc.subject | POSTMENOPAUSAL | |
dc.subject | THERAPY | |
dc.subject | EFFICACY | |
dc.title | Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen-receptor positive endocrine-resistant and fulvestrant-resistant breast cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-10-07 | |
dc.date.updated | 2023-02-21T13:33:12Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41523-022-00483-1 | |
rioxxterms.licenseref.startdate | 2022-11-29 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36446866 | |
pubs.issue | 1 | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrine Therapy Resistance | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Endocrinology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41523-022-00483-1 | |
pubs.volume | 8 | |
icr.researchteam | Endocrine Therapy Resist | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Schuster, Eugene | |
icr.provenance | Deposited by Mr Arek Surman on 2023-02-21. Deposit type is initial. No. of files: 1. Files: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen-receptor positive endocrine-resistant and.pdf | |