Zebrafish Screening Identifies Erlotinib as a Wnt/β-Catenin Inhibitor in T-ALL, Biomedicine and Pharmacotherapy (2024)

The Wnt/β-catenin pathway is important in cancer and stem cell biology, making it a potential target for therapy. However, using Wnt inhibitors in the clinic is difficult due to off-target effects and interactions with other pathways. In this study, we used a zebrafish model to screen 773 FDA-approved drugs to find Wnt/β-catenin inhibitors with low toxicity. Using zebrafish with a Wnt reporter, we identified several drugs that inhibited Wnt signaling without affecting zebrafish development. Erlotinib was the most effective drug and also worked in human cells by blocking Wnt/β-catenin signaling. In human T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, Erlotinib reduced self-renewal and the frequency of leukemia-initiating cells, delaying disease formation in zebrafish models. This study underscores the importance of zebrafish in drug discovery and highlights Erlotinib’s potential as a Wnt inhibitor for cancers driven by abnormal Wnt/β-catenin signaling.

DOI: https://doi.org/10.1016/j.biopha.2023.116013