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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 Antonio-
dc.contributor.authorRodriguez Lajusticia, Laura-
dc.contributor.authorMalon, Diego-
dc.contributor.authorMalumbres, Marcos-
dc.contributor.authorquintela-fandino, miguel-
dc.identifier.citation1. Mouron S, Bueno MJ, Munoz M, Torres R, Rodriguez S, Apala JV, Silva J, Sanchez-Bayona R, Manso L, Guerra Martinez JA, Rodriguez Lajusticia L, Malon Gimenez D, Malumbres M, Quintela Fandino MA. p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast cancer. JNCI Cancer Spectr. 2023;7(2):pkad014. doi: 10.1093/jncics/pkad014. PMID: 36806942.es_ES
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.description.sponsorshipAsociación Española contra el Cánceres_ES
dc.publisherOxford University Press (OUP)es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 España*
dc.subject.meshCyclin-Dependent Kinase 4es_ES
dc.subject.meshProtein Kinase Inhibitorses_ES
dc.subject.meshBreast Neoplasmses_ES
dc.titlep27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast canceres_ES
dc.contributor.funderAsociación Española contra el Cánceres_ES
dc.identifier.journalJNCI cancer spectrumes_ES
dc.identifier.journalabbreviationJNCI Cancer Spectres_ES
dc.contributor.authoraffiliationServicio de Oncología Médica. Hospital Universitario de Fuenlabradaes_ES
dc.subject.decsQuinasa 4 Dependiente de la Ciclinaes_ES
dc.subject.decsInhibidores de Proteínas Quinasases_ES
dc.subject.decsNeoplasias de la Mamaes_ES
Appears in Collections:Hospitales > H. U. de Fuenlabrada > Artículos

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