Publication:
p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast cancer.

Simple item page
dc.contributor.authorMouron, Silvana
dc.contributor.authorBueno, Maria J
dc.contributor.authorMuñoz, Manuel
dc.contributor.authorTorres, Raul
dc.contributor.authorRodríguez, Sandra
dc.contributor.authorApala, Juan V
dc.contributor.authorSilva, Jorge
dc.contributor.authorSánchez-Bayona, Rodrigo
dc.contributor.authorManso, Luis
dc.contributor.authorGuerra, Juan
dc.contributor.authorRodriguez-Lajusticia, Laura
dc.contributor.authorMalon, Diego
dc.contributor.authorMalumbres Martinez, Marcos
dc.contributor.authorQuintela Fandino, Miguel Angel
dc.date.accessioned2024-06-12T09:04:09Z
dc.date.available2024-06-12T09:04:09Z
dc.date.issued2023-03-01
dc.description.abstractCDK4/6 inhibitors benefit a minority of patients who receive them in the breast cancer adjuvant setting. p27Kip1 is a protein that inhibits CDK/Cyclin complexes. We hypothesized that single-nucleotide polymorphisms that impaired p27Kip1 function could render patients refractory to endocrine therapy but responsive to CDK4/6 inhibitors, narrowing the patient subpopulation that requires CDK4/6 inhibitors. We found that the p27Kip1 V109G single-nucleotide polymorphism is homozygous in approximately 15% of hormone-positive breast cancer patients. Polymorphic patients experience rapid failure in response to endocrine monotherapy compared with wild-type or heterozygous patients in the first-line metastatic setting (progression-free survival: 92 vs 485 days, P < .001); when CDK4/6 inhibitors are added, the differences disappear (progression-free survival: 658 vs 761 days, P = .92). As opposed to wild-type p27Kip1, p27Kip1 V109G is unable to suppress the kinase activity of CDK4 in the presence of endocrine inhibitors; however, palbociclib blocks CDK4 kinase activity regardless of the p27Kip1 status. p27Kip1 genotyping could constitute a tool for treatment selection.es_ES
dc.format.number2es_ES
dc.format.volume7es_ES
dc.identifier.citationJNCI Cancer Spectr . 2023;7(2):pkad014.es_ES
dc.identifier.doi10.1093/jncics/pkad014es_ES
dc.identifier.e-issn2515-5091es_ES
dc.identifier.journalJNCI cancer spectrumes_ES
dc.identifier.pubmedID36806942es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/19749
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Cáncer de Mamaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshBreast Neoplasmses_ES
dc.subject.meshFemalees_ES
dc.subject.meshHumanses_ES
dc.subject.meshBiomarkerses_ES
dc.subject.meshCyclin-Dependent Kinase 4es_ES
dc.subject.meshProtein Kinase Inhibitorses_ES
dc.titlep27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast cancer.es_ES
dc.typeotheres_ES
dspace.entity.typePublication
relation.isAuthorOfPublication6b047387-7d93-4af5-b19a-e17b3eabedd6
relation.isAuthorOfPublicationf95b0d37-00ac-4524-a4b2-c2c988784d1f
relation.isAuthorOfPublication.latestForDiscovery6b047387-7d93-4af5-b19a-e17b3eabedd6
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
p27Kip1V109Gasabiomarker_2023.pdf
Size:
569.58 KB
Format:
Adobe Portable Document Format
Description:
Artículo principal
Download
Collections
Grupos de investigación