Abstract 368: Unique breast cancer CDX panels for KAT6, ER, and CDK4/6

Abstract Estrogen receptor-positive (ER+) breast cancer accounts for approximately 75% of all breast cancers. Over-expression of lysine acetyltransferase 6A (KAT6A), a histone acetyltransferase (HAT), shared a proportion of 10-15% in breast cancer patients and increased the tumor growth through binding the promoter region to enhance ER expression level. Inhibitors of KAT6A were thought to be anti-tumorigenic by deregulation of ER expression. In addition, the cyclin-dependent kinases 4/6-cyclinD-Rb (CDK4/6-cyclinD-Rb) pathway is very important and crucial for ER downstream signaling in ER+ breast cancers. To accelerate the discovery of anti-ER+ breast cancer drugs through KAT6A and CDK4/6 pathways, we generated four specific CDX models which cover the most popular ER+/KAT6A cell lines (BT-474, ZR-75-1) and ER+/ CDK4/6 cell lines (MCF-7, HCC1428) and revealed the efficacy of KAT6A inhibitor (PF-9363), CDK4/6 inhibitor (Palbociclib), or ER inhibitor (Fulvestrant) on these breast CDX models. The in vivo MOA of these inhibitors were also evaluated by Western Blotting and pathological examination. Citation Format: Tianyu Pang, Haiting Dai, Ziwei Li, Wenbo Du, Wen-Jen Yu. Unique breast cancer CDX panels for KAT6, ER, and CDK4/6 [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 368.