Many human cancers do not respond to treatment and often times those that initially respond eventually acquire drug resistance. Our lab uses high-throughput screening technology in combination with tractable pre-clinical mouse models to investigate basic mechanisms of intrinsic and acquired drug resistance. We also use genetic and computational tools to understand the how cancer therapies exert their effects and how to best combine drugs to achieve greater efficacy and preempt the evolution of chemoresistance. Our goal is to identify novel cancer drug targets, as well as strategies for tailoring drug regimens to target protective mechanisms used by cancers to evade and escape cancer therapy.