Abstract 3769: Continuous, low intensity systemic dosing maximizes the therapeutic margin of Eg5/KSP inhibition in an orthotopic model of urothelial cell carcinoma

Urothelial Cell Carcinoma (UCC) is the fifth most common cancer, but no new generation molecularly targeted therapies have been registered to treat this disease. Non muscle-invasive bladder cancer can be treated by systemic or intravesical dosing routes. However, the urothelium is one of the most formidable permeability barriers in nature, and may limit the penetration of small molecules into tumour tissue from the intravesical location. Inhibitors of mitosis, including spindle proteins such as Eg5, are attractive targets for cancer therapy, but their efficacy when dosed systemically is severely limited by bone marrow toxicities such as neutropenia and thrombocytopenia. AZ9814, a very potent and selective small molecule inhibitor of Eg5, induces apoptosis and inhibits proliferation of UCC cells in culture with a GI50 of Citation Format: Leigh Williams, Rebecca Ellston, Dawn Trueman, Helen Musgrove, Linette Ruston, Brian Aquila, Elizabeth Pease, Stephanie Klein, Barry R. Davies. Continuous, low intensity systemic dosing maximizes the therapeutic margin of Eg5/KSP inhibition in an orthotopic model of urothelial cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3769.