Cancer

Cell culture and mouse studies suggest combining Votrient pazopanib and a potassium channel inhibitor could help treat rhabdoid tumors. High throughput screening of a library of approved drugs in six human rhabdoid tumor cell lines and one human medulloblastoma cell line with the rhabdoid tumor marker SMARCB1 knocked out, identified the broad-spectrum tyrosine kinase inhibitor Votrient and the potassium channel inhibitor clofilium tosylate as inhibitors of cell growth (median IC₅₀ values of 0.8 μM and 4.2 μM, respectively) that increased apoptosis compared with vehicle. In two patient-derived xenograft (PDX) mouse models of rhabdoid tumors, Votrient plus clofilium tosylate decreased tumor cell proliferation and tumor volume and increased survival compared with vehicle. Next steps could include testing the safety of the combination therapy in animal models.

Novartis AG markets Votrient, a broad-spectrum inhibitor of VEGF and other tyrosine kinases, for renal cancer and sarcoma and has the compound in registration for ovarian cancer and Phase II testing for multiple other solid tumor types. ...