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Abstract
Potent and specific kinase inhibitors have revolutionized the treatment of kinase-driven cancers by providing targeted inhibition of known cancer driving kinases. However, disease resistance and disease persistence have prevented targeted kinase therapy from being curative. Depending upon the disease state, kinase inhibitors may be effective for many years or only a few months before secondary resistance develops. Even for diseases where treatment is efficacious for many years, patients must be treated continuously, as interruption of the therapy results in disease growth within a few weeks or months. The goal of this thesis work was to address both disease resistance and persistence in KIT-mutant mast cell cancer models through the development of novel combination therapies.