p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases

Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16(INK4A) is deficient in the majority of HER2+ BCBMs. p16(INK4A)-deficiency as measured by protein immunohistochemistry predicted response to comb...

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Autores principales: Ni, Jing, Kabraji, Sheheryar, Xie, Shaozhen, Wang, Yanzhi, Pan, Peichen, He, Xiaofang, Liu, Zongming, Leone, Jose Palbo, Long, Henry W., Brown, Myles A., Winer, Eric P., Dillon, Deborah A. R., Lin, Nancy U., Zhao, Jean J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933392/
https://www.ncbi.nlm.nih.gov/pubmed/35304445
http://dx.doi.org/10.1038/s41467-022-29081-2
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author Ni, Jing
Kabraji, Sheheryar
Xie, Shaozhen
Wang, Yanzhi
Pan, Peichen
He, Xiaofang
Liu, Zongming
Leone, Jose Palbo
Long, Henry W.
Brown, Myles A.
Winer, Eric P.
Dillon, Deborah A. R.
Lin, Nancy U.
Zhao, Jean J.
author_facet Ni, Jing
Kabraji, Sheheryar
Xie, Shaozhen
Wang, Yanzhi
Pan, Peichen
He, Xiaofang
Liu, Zongming
Leone, Jose Palbo
Long, Henry W.
Brown, Myles A.
Winer, Eric P.
Dillon, Deborah A. R.
Lin, Nancy U.
Zhao, Jean J.
author_sort Ni, Jing
collection PubMed
description Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16(INK4A) is deficient in the majority of HER2+ BCBMs. p16(INK4A)-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM.
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spelling pubmed-89333922022-04-01 p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases Ni, Jing Kabraji, Sheheryar Xie, Shaozhen Wang, Yanzhi Pan, Peichen He, Xiaofang Liu, Zongming Leone, Jose Palbo Long, Henry W. Brown, Myles A. Winer, Eric P. Dillon, Deborah A. R. Lin, Nancy U. Zhao, Jean J. Nat Commun Article Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16(INK4A) is deficient in the majority of HER2+ BCBMs. p16(INK4A)-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM. Nature Publishing Group UK 2022-03-18 /pmc/articles/PMC8933392/ /pubmed/35304445 http://dx.doi.org/10.1038/s41467-022-29081-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ni, Jing
Kabraji, Sheheryar
Xie, Shaozhen
Wang, Yanzhi
Pan, Peichen
He, Xiaofang
Liu, Zongming
Leone, Jose Palbo
Long, Henry W.
Brown, Myles A.
Winer, Eric P.
Dillon, Deborah A. R.
Lin, Nancy U.
Zhao, Jean J.
p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title_full p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title_fullStr p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title_full_unstemmed p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title_short p16(INK4A)-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
title_sort p16(ink4a)-deficiency predicts response to combined her2 and cdk4/6 inhibition in her2+ breast cancer brain metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933392/
https://www.ncbi.nlm.nih.gov/pubmed/35304445
http://dx.doi.org/10.1038/s41467-022-29081-2
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