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Title: p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast cancer
Filiation: Servicio de Oncología Médica. Hospital Universitario de Fuenlabrada
Issue Date: 12-Feb-2023
Publisher: Oxford University Press (OUP)
Citation: 1. 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.
Abstract: CDK4/6 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.
PMID: 36806942
Rights: info:eu-repo/semantics/openAccess
Atribución-NoComercial-CompartirIgual 3.0 España
ISSN: 2515-5091
Appears in Collections:Hospitales > H. U. de Fuenlabrada > Artículos

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