Abstract 223: High-throughput drug discovery against breast cancer stem cells

Abstract

Abstract The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Clinically, CSCs are predicted to mediate tumor recurrence after chemotherapy and radiotherapy due to the relative inability of these modalities to effectively target CSCs. Therefore, new therapies that target CSC must be developed and combined with standard therapy to achieve a true cure. Targeting breast CSC represents an attractive avenue for developing therapeutics; however, there are multiple pools of breast CSCs utilizing distinct signaling pathways, such as Wnt/β-catenin & NF-κB. These breast CSC pools are identified using flow cytometry as cells with high expression of aldehyde dehydrogenase (ALDH), CD44+CD24-, or CD90+. We have developed a high-throughput flow cytometry based screen against CD90+ breast CSCs. We screened ∼18,500 small molecules for inhibitors of CD90+ frequency and identified 19 compounds. Here, we will present data examining this compounds against ALDH+, and CD44+CD24- breast CSCs. By identifying compounds with that target multiple pools of breast CSCs, these compounds might be exploited in future drug development endeavors. Citation Format: Sean P. McDermott, Fatou Ndaw, Alexandra Fox, Steve R. Vander Roest, Martha J. Larsen, Max S. Wicha. High-throughput drug discovery against breast cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 223. doi:10.1158/1538-7445.AM2014-223