Cancer stem cells (CSCs) are thought to play significant roles in breast cancer initiation and progression. Conventional therapeutic agents target tumor bulk but spare CSCs, leading to tumor recurrence and relapse. Therefore, drugs that eliminate both tumor bulk and CSCs may represent the most effective treatment strategy for breast cancer. We have developed a proprietary cell-based screen called StemScreen® that permits the rapid testing and identification of novel CSC-directed compounds in a high-throughput manner. StemScreen® takes advantage of a landmark discovery that many cancer cell lines harbor stable populations of CSCs. Our initial studies utilized a breast cancer cell line transfected with a unique expression vector that is only active in the 1-5% putative CSC population. The StemScreen® platform is unique because it allows for screening of compounds within the context of the CSCs’ natural microniche environment and has advantages over traditional drug discovery methods that have been designed to identify compounds that only target tumor bulk, but not CSCs.
In an effort to increase the throughput and make the assay compatible with existing compound libraries, we miniaturized the platform to a 384-well format and optimized the line for high-content screening. A series of compound hits identified from screening these cells against smaller libraries of known active compounds as well as larger and more diverse compound libraries will be presented. We are also currently expanding this technology into other tumor types. We believe that this approach represents a major technological advance in oncology drug discovery and that this platform will be instrumental in the discovery of unique new therapies that have a dual effect on CSCs and non-CSC tumor bulk.
Citation Format: Janice Chen, Hai Li, Marcie A Glicksman, Charles Karan, Christopher Brooks, Eric K Rowinsky. StemScreen®, an innovative platform technology for the identification of novel cancer stem cell-directed compounds [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-07.