Identification of Novel Molecules Targeting Cancer Stem Cells

Multiple studies focused on tumor heterogeneity and cellular hierarchies have demonstrated the role of cancer stem cells (CSC) in tumor initiation and recurrence. Colorectal cancer is one of the leading causes of cancer-related death and is hierarchically organized, with the majority of tumor cells descending from a small population of colon cancer stem cells (CCSCs). Such a rare self-renewing population is marked by the acquisition of distinct chromatin regulation and transcriptional programs. Fundamental molecular deviations between CCSCs and bulk tumor cells as well as normal tissues represent a unique therapeutic access to develop novel, selective anticancer therapies.In this chapter, we describe a methodological pipeline to identify novel molecules to selectively target human CCSC. We present a point-by-point description of a typical phenotypic molecular screening experiment, aiming to identify selective modulators of human CCSCs vs. normal intestinal progenitor cells.