Nomura M, et al. - The antitumor activity of Tegavivint, a novel β-catenin/transducing β-like protein 1 (TBL1) inhibitor, against osteosarcoma (OS) was assessed via employing in vitro, ex vivo and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high-risk disease. In vitro findings suggested anti-proliferative activity of Tegavivint against OS cells. Ex vivo findings suggested an active reduction in micro- and macrometastatic development with Tegavivint. They observed that Tegavivint led to the suppression of multiple OS PDX tumors (n = 3), including paired patient primary and lung metastatic tumors with inherent chemoresistance, in vivo. In addition, Tegavivint was noted suppressing increased stem cell signatures, including enhanced concomitant aldehyde dehydrogenase (ALDH1) and β-catenin expression and downstream activity, which are exhibited by metastatic lung OS cell lines (n = 2). These findings suggest that for advanced stages of OS, Tegavivint is a promising therapeutic agent via its targeting of the β-catenin/ALDH1 axis.