dc.contributor.author | Zhu, Z | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Loi, S | |
dc.contributor.author | André, F | |
dc.contributor.author | Martin, M | |
dc.contributor.author | Diéras, V | |
dc.contributor.author | Gelmon, KA | |
dc.contributor.author | Harbeck, N | |
dc.contributor.author | Zhang, C | |
dc.contributor.author | Cao, JQ | |
dc.contributor.author | Yan, Z | |
dc.contributor.author | Lu, DR | |
dc.contributor.author | Wei, P | |
dc.contributor.author | VanArsdale, TL | |
dc.contributor.author | Rejto, PA | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Rugo, HS | |
dc.contributor.author | Loibl, S | |
dc.contributor.author | Cristofanilli, M | |
dc.contributor.author | Finn, RS | |
dc.contributor.author | Liu, Y | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-10-18T09:52:58Z | |
dc.date.available | 2022-10-18T09:52:58Z | |
dc.date.issued | 2022-08-16 | |
dc.identifier | ARTN 56 | |
dc.identifier | 10.1038/s41698-022-00297-1 | |
dc.identifier.citation | npj Precision Oncology, 2022, 6 (1), pp. 56 - | en_US |
dc.identifier.issn | 2397-768X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5545 | |
dc.identifier.eissn | 2397-768X | |
dc.identifier.eissn | 2397-768X | |
dc.identifier.doi | 10.1038/s41698-022-00297-1 | |
dc.description.abstract | While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor-positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135). | en_US |
dc.format | Electronic | |
dc.format.extent | 56 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | NATURE PORTFOLIO | en_US |
dc.relation.ispartof | npj Precision Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Science & Technology | en_US |
dc.subject | Life Sciences & Biomedicine | en_US |
dc.subject | Oncology | en_US |
dc.subject | ESTROGEN-RECEPTOR | en_US |
dc.subject | BREAST-CANCER | en_US |
dc.subject | TUMOR MICROENVIRONMENT | en_US |
dc.subject | ENDOCRINE RESISTANCE | en_US |
dc.subject | THERAPY | en_US |
dc.subject | MECHANISMS | en_US |
dc.subject | DISCOVERY | en_US |
dc.title | Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-06-20 | |
dc.date.updated | 2022-10-18T09:52:21Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s41698-022-00297-1 | en_US |
rioxxterms.licenseref.startdate | 2022-08-16 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35974168 | |
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/Breast Cancer Research/Molecular Oncology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41698-022-00297-1 | |
pubs.volume | 6 | |
icr.researchteam | Molecular Oncology | en_US |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman on 2022-10-18. Deposit type is initial. No. of files: 1. Files: Comparative biomarker analysis of PALOMA-23 trials for palbociclib.pdf | |