p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Abstract
Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16INK4A is deficient in the majority of HER2+ BCBMs. p16INK4A-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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 18, 2022
- Source ID
- 10.1038/s41467-022-29081-2
Entities
People
- Deborah A. R. Dillon
- Eric Winer
- Henry W Long
- Jean J. Zhao
- Jing Ni
- Jose Palbo Leone
- Myles A. Brown
- Nancy U Lin
- Peichen Pan
- Shaozhen Xie
- Sheheryar Kabraji
- Xiaofang He
- Yanzhi Wang
- Zongming Liu
Organizations
- National Institutes of Health
- The Breast Cancer Research Foundation
- United States Department of Defense
- United States Department of Health and Human Services