High‐Throughput Drug Screening Identifies Pazopanib and Clofilium Tosylate As Promising Treatments for Malignant Rhabdoid Tumors

The poor prognosis of rhabdoid tumors (RT) justifies the search for new therapies. By a high‐throughput drug screening and subsequent in vitro confirmation of selected drugs, we identified as good SMARCB1‐dependent therapeutic candidates, broad inhibitors of tyrosine kinase receptors (RTK) such as pazopanib, and the potassium channel inhibitor clofilium tosylate (CfT). Their combination significantly induced RT apoptotic cell death in vitro. A human phospho‐kinase antibody array revealed PDGFRα/β and FGFR2 as pazopanib targets, while these genes were the most highly expressed RTK in our primary tumor data set. Of note, combined genetic inhibition of at least two RTK was only partially able to recapitulate the effect of pazopanib, emphasizing the requirement of broad inhibition. We then showed that pazopanib treatment reduced tumor growth in vivo while its combination with CfT could at least recapitulate the efficiency of conventional chemotherapy. Altogether, these results may influence future clinical trials for RT.