Abstract 3506: Targeting breast cancer stem cells and non-stem breast cancer cells through combination therapies

Abstract

Abstract Cancer stem cells (CSCs), as a subset of tumor cells with enhanced capacity to generate tumors, have recently been attributed to driving cancer recurrence and metastasis. Although the current CSC model highlights the importance of developing strategies to target CSCs, it is conceivable that the depletion of CSCs within a tumor would not lead to complete regression since non-CSCs might still be capable of sustaining tumor growth or regaining CSC potential. As either of these possibilities would confound the effectiveness of therapeutic agents that exclusively target CSCs, we aimed to rapidly identify combination therapies that could synergistically target both breast cancer cells and breast CSCs. Using a comprehensive small chemical library screen consisting of more than 1600 compounds, we identified a total of 193 small molecules, including 45 FDA approved drugs, which could target both breast CSCs and non-CSCs. When combined with conventional chemotherapeutic agents (e.g. cisplatin, doxorubicin or paclitaxel), histone deacetylase (HDAC) inhibitors exhibited significant synergistic effects in targeting both breast CSCs and non-CSCs. In summary, our data suggests that HDAC inhibitors represent a class of agents that could synergize with chemotherapeutic agents in refractory breast cancer cells and warrant further investigations. Citation Format: Ling-Wei Hii, Felicia Fei-Lei Chung, Boon-Shing Tan, Yang Mooi Lim, Soon-Keng Cheong, Chee-Onn Leong. Targeting breast cancer stem cells and non-stem breast cancer cells through combination therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3506. doi:10.1158/1538-7445.AM2015-3506