Abstract PD7-01: Bromodomain protein 3 is a novel therapeutic target in invasive lobular carcinoma

摘要: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising 10% tumours. ILC characterised by loss E-cadherin, and generally estrogen receptor (ER) positive. The majority cancers are treated with endocrine therapy, although approximately one in three women de novo resistant to therapy. To identify novel therapeutic targets for the treatment ILC, we carried out RNA sequencing on 61 primary samples. We found that high expression epigenetic reader, bromodomain protein 3 (BRD3) was associated poor recurrence free survival. also validated this finding separate cohort 99 patient samples using METABRIC cohort. Next, assessed cell lines sensitivity JQ1, an inhibitor BET family proteins. JQ1 inhibited growth all tested. Interesting, two were sensitive JQ1-induced apoptosis, whereas inherently apoptosis. Using dynamic BH3 profiling showed dependent anti-apoptotic BCL-XL following treatment. Interestingly, show both 2D 3D cultures synergistic when combined mimetic, ABT-263. Highlighting combination ABT-263 may be potential option ILC. unveil mechanism underlying resistance performed paired-end compared differentially expressed genes lines. DAVID gene ontology analysis identified 6 pathways upregulated line including MAPK, Wnt, insulin signaling. lines, which inhibition demonstrated levels FGFR1-4 at mRNA level level. Combination FGFR1 PD173074 or knockdown FGFR siRNA, resulted increased death cells. Currently, assessing how signaling enables survival cells determining exact function BRD3 In conclusion, have target, BRD3, mimetic more effective strategy Citation Format: Haley K, Walsh L, Moran B, Das S, Tarrant F, Caldas C, Bernards R, Gallagher W, O9Connor D, Ni Chonghaile T. Bromodomain target invasive [abstract]. In: Proceedings 2018 San Antonio Breast Cancer Symposium; Dec 4-8; Antonio, TX. Philadelphia (PA): AACR; Res 2019;79(4 Suppl):Abstract nr PD7-01.