Abstract 6778: Targeting the YAP-TEAD interaction in brain metastatic breast cancer cells

Abstract Breast cancer metastasis to the brain is a devastating stage of breast cancer that presents with cognitive decline and seizures, and currently there are no treatments available. Brain metastases are resistant to immunotherapy, chemotherapy, and targeted therapies. This is partly because the blood-brain barrier and the blood-tumor barriers prevent effective delivery of these treatment modalities at clinically safe doses and partly because we do not know enough about the molecular mechanisms that govern breast cancer brain metastasis. Recent work in mouse models of breast cancer brain metastases revealed that the interaction between Yes Associated Protein (YAP) and Transcriptional Enhanced Association Domain (TEAD) family of transcription factors is an essential step in outgrowth of disseminated cancer cells. Here, we demonstrate a series of time-lapse imaging assays and luminescence based viability assays that we optimized to investigate the impact of YAP-TEAD inhibitors and chemotherapeutic agents on the viability of brain metastatic breast cancer cells in vitro. Our results will guide the prioritization of these treatment modalities in pre-clinical in vivo models. We will specifically investigate whether one or more of these agents can be loaded onto nanoparticle-engineered macrophages to better overcome blood-brain and blood-tumor barriers for effective delivery and targeted destruction of brain metastases. Citation Format: Caitlyn C. Castillo, Mohamed Haloul, Philana Phan, Zongmin Zhao, Ekrem E. Er. Targeting the YAP-TEAD interaction in brain metastatic breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6778.