Abstract

Cancer arises through an evolutionary process whereby normal cells acquire mutations that erode growth controls, leading to the expansion of aberrantly proliferating cells. Such mutations activate oncogenes or inactivate tumor suppressors, each bestowing new capabilities to emerging tumors. Still, cancer is not an inevitable consequence of mutation but is instead kept in check by intrinsic tumor-suppressor programs activated in damaged cells. Accordingly, our laboratory studies such mechanism in order to reveal key regulatory nodes controlling basic cellular processes and to identify the strategies nature uses to combat cancer. More recently, our interests have expanded to explore the action of tumor maintenance genes – those genes needed to sustain the proliferation and survival of malignant cancer cells – with the goal of dentifying cancer vulnerabilities and therapeutic targets. Our approach combines powerful mouse models, genetics, and genomics in a coordinated manner that allows us to study tumor suppressor and tumor maintenance networks in a comprehensive way. Recent efforts to characterize tumor suppressor gene action and the consequences of tumor suppressor gene loss will be discussed.