Resumen
Cancer stem cells (CSCs) are thought to be involved in tumor initiation and recurrence, which makes them pivotal therapeutic targets. However, the molecular circuits behind CSC characteristics are not fully understood and the low number of CSCs is an obstacle for conducting tests that explore their properties. Thus, increasing the number of these cells via small molecule-mediated cellular reprogramming seems a valid alternative tool. Using the SORE6-GFP reporter system, based on SOX2/OCT4 activity and incorporated in gastric non-CSCs, we performed a high-throughput drug screen to identify small molecules capable of converting non-CSCs into CSCs. Our results show that ciclopirox olamine (CPX) is able to reprogram gastric cancer cells to a stem-like phenotype via SOX2 expression, reprogram cell metabolism, and induce senescence. Furthermore, these results suggest that the CSC phenotype is a resistance mechanism to CPX treatment, which is being considered as a repurposing drug for cancer treatment.