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Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to largely ineffective therapeutics available for this disease. Recently, inhibitors of bromodomain and extraterminal domain (BET) inhibitors have been shown to… Click to show full abstract
Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to largely ineffective therapeutics available for this disease. Recently, inhibitors of bromodomain and extraterminal domain (BET) inhibitors have been shown to have therapeutic efficacy against various malignancies, including PDA. Here we present data on sensitivity of PDA patient-derived organoids (PDO) to a novel dual BET and CBP/P300 inhibitor, NEO2734 (Epigene Therapeutics Inc.). Our cell viability screen on a panel of 30 PDOs derived from PDA patient and xenograft tumor tissue revealed differential drug sensitivities to NEO2734 inhibitor. Antitumor effect of NEO2734 on the most sensitive PPTO.2 model was further confirmed in vivo using patient-derived xenograft PPTO.2 model. To identify potential biomarkers associated with differential sensitivities of PDA PDOs to NEO2734 inhibitor, we generated gene expression profiles from 13 PDOs derived from primary patient tumors. Using the probabilistic concordance index (C-index), 13 genes (Bonferroni corrected P Citation Format: Nikolina Radulovich, Laura Tamblyn, Heewon Seo, Benjamin Haibe-Kains, Mathieu Lupien, Francis Gilles, Ming S. Tsao. Targeting pancreatic cancer organoids with dual BET and CBP/P300 inhibitor NEO2734 [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B46.