Cancer arises through an evolutionary process in which normal cells acquire mutations that erode growth controls, leading to the expansion of aberrantly proliferating cells. Such mutations activate oncogenes or inactivate tumor suppressors, bestowing new capabilities to developing cancer cells. Our research is based on the premise that the path of cancer evolution dictates a tumor’s subsequent response to therapy and creates unique vulnerabilities that represent therapeutic opportunities.
We use mouse models, RNA interference (RNAi), and cancer genomics to identify components of tumor suppressor gene networks and understand the molecular determinants of treatment response. We also use temporally regulatable RNAi technology to identify genes required for tumor maintenance and to explore the mechanisms involved in tumor regression, including both cell intrinsic and extrinsic mechanisms.
Our goal is to gain a more comprehensive understanding of tumor suppressor networks and identify cancer maintenance genes that will be useful therapeutic targets relevant to specific cancer genotypes.