Exploring the cancer stem cell phenotype with high-throughput screening applications

Several human cancer types consist of diverse cell populations that can differ in their tumor-driving potential. One breakthrough has been the identification of poorly differentiated tumor cells, herein termed cancer stem cells (CSCs). CSCs have been shown to initiate tumors in different model systems and have been implicated in cancer resistance to conventional therapies. The clinical relevance of CSCs has been increasingly recognized, and recent progress in their enrichment and characterization has paved the way for exploring CSC biology with high-throughput screening technologies. This article focuses on functional chemical and RNAi screens that have led to the identification of factors that control the CSC phenotype. Different experimental strategies, current challenges and perspectives in CSC drug discovery are discussed.