Aspects of the disclosure relate to methods that involve activating the Protein Kinase A (PKA) pathway to induce cancer stem cells (CSCs) to undergo a mesenchymal to epithelial transition. Methods provided herein are useful, in some embodiments, because they render CSCs amenable to treatment with conventional cancer therapies. In some embodiments, methods are provided that involve assaying PKA pathway activity to identify compounds that selectively target CSCs.