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http://hdl.handle.net/2445/202133
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DC Field | Value | Language |
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dc.contributor.author | Guerrero Zotano, Ángel | - |
dc.contributor.author | Belli, Stefania | - |
dc.contributor.author | Zielinski, Christoph | - |
dc.contributor.author | Gil Gil, Miguel | - |
dc.contributor.author | Fernández Serra, Antonio | - |
dc.contributor.author | Ruíz Borrego, Manuel | - |
dc.contributor.author | Ciruelos Gil, Eva María | - |
dc.contributor.author | Pascual, Javier | - |
dc.contributor.author | Muñoz Mateu, Montserrat | - |
dc.contributor.author | Bermejo, Begoña | - |
dc.contributor.author | Margeli Vila, Mireia | - |
dc.contributor.author | Antón, Antonio | - |
dc.contributor.author | Murillo, Laura | - |
dc.contributor.author | Nissenbaum, Bella | - |
dc.contributor.author | Liu, Yuan | - |
dc.contributor.author | Herranz, Jesús | - |
dc.contributor.author | Fernández García, Daniel | - |
dc.contributor.author | Caballero, Rosalía | - |
dc.contributor.author | López Guerrero, José Antonio | - |
dc.contributor.author | Bianco, Roberto | - |
dc.contributor.author | Formisano, Luigi | - |
dc.contributor.author | Turner, Nicholas | - |
dc.contributor.author | Martín, Miguel | - |
dc.date.accessioned | 2023-09-21T12:29:24Z | - |
dc.date.available | 2023-09-21T12:29:24Z | - |
dc.date.issued | 2023-04-14 | - |
dc.identifier.issn | 1557-3265 | - |
dc.identifier.uri | http://hdl.handle.net/2445/202133 | - |
dc.description.abstract | Purpose: In hormone receptor???positive (HR+)/HER2- meta-static breast cancer (MBC), it is imperative to identify patients who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/ 6i) and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting, but further validation is needed. Experimental Design: We performed mRNA gene expression profiling and correlation with progression-free survival (PFS) on 455 tumor samples included in the phase III PEARL study, which assigned patients with HR+/HER2-MBC to receive palbociclib+endocrine therapy (ET) versus capecitabine. Estrogen receptor???positive (ER+)/ HER2-breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET. Results: Non-luminal subtype was more prevalent in meta-static (14%) than in primary tumor samples (4%). Patients with??non-luminal tumors had median PFS of 2.4 months with palbociclib+ET and 9.3 months with capecitabine; HR 4.16, adjusted P value < 0.0001. Tumors with high CCNE1 expression (above median) also had worse median PFS with palbociclib+ET (6.2 months) than with capecitabine (9.3 months); HR 1.55, adjusted P value = 0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile), we found higher levels of Polo-like kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2-cell line models, we show that PLK1 inhibition reverses resistance to palbociclib+ET. Conclusions: We confirm the association of non-luminal sub-type and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Association for Cancer Research (AACR) | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1158/1078-0432.CCR-22-2206 | - |
dc.relation.ispartof | Clinical Cancer Research, 2023, vol. 29, num. 8, p. 1557-1568 | - |
dc.relation.uri | https://doi.org/10.1158/1078-0432.CCR-22-2206 | - |
dc.rights | cc by-nc-nd (c) Guerrero Zotano, Ángel et al., 2023 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Receptors d'hormones | - |
dc.subject.classification | Oncogens | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Hormone receptors | - |
dc.subject.other | Oncogenes | - |
dc.title | CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2−Metastatic Breast Cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2023-09-05T13:01:01Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36749874 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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PIIS2211124723005442 (1).pdf | 5.07 MB | Adobe PDF | View/Open |
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