p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor–positive breast cancer

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...

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Published in:JNCI cancer spectrum 2023-03, Vol.7 (2)
Main Authors: Mouron, Silvana, Bueno, Maria J, Muñoz, Manuel, Torres, Raul, Rodríguez, Sandra, Apala, Juan V, Silva, Jorge, Sánchez-Bayona, Rodrigo, Manso, Luis, Guerra, Juan, Rodriguez-Lajusticia, Laura, Malon, Diego, Malumbres, Marcos, Quintela-Fandino, Miguel
Format: Article
Language:English
Subjects:
Biomarkers
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Brief Communications
Cyclin-Dependent Kinase 4 - genetics
Cyclin-Dependent Kinase 4 - metabolism
Female
Humans
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
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Summary: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 
ISSN:2515-5091
2515-5091
DOI:10.1093/jncics/pkad014