Program Co-Leaders Charles Craik, PhD Kevan Shokat, PhD

The Chemistry and Cancer Program is a multidisciplinary effort, involving nearly 20 chemists, cancer biologists, and cancer physicians, to develop new chemical approaches for diagnosing, preventing, and treating all forms of human cancer.

Advances in our understanding of the molecular basis of cancer have provided many new potential approaches for therapy. Since most new cancer therapies are based on drugs, chemists have a clear role in the process of discovery and exploitation of new anti-cancer targets. Collaborations with scientists in other Cancer Center programs are likely to lead to new insights and the creation of novel therapies. Overall, the goal of the program in Chemistry and Cancer is to foster such collaborations at the interface of the chemical sciences and cancer biology.

The program is organized around three protein target classes: proteases, nuclear hormone receptors, and protein kinases. These three classes of enzymes are intimately involved in all aspects of cell signaling and are currently targets of a number of anti-cancer agents both in current use and in clinical trials. Members of the Chemistry and Cancer Program are leading experts in the study of these three classes of enzymes in terms of basic biological functions of these proteins, their three-dimensional structure, and their biochemical characterization in terms of substrate specificity or gene regulatory properties, as well as discovery of highly potent inhibitors of individual members of these families.

The purpose of the Chemistry and Cancer Program is to apply the understanding of both the chemistry and biology of these three classes of enzymes to defined problems in cancer biology. Through interactions and collaborations both within the program and among other Cancer Center research efforts, Chemistry and Cancer investigators have initiated a number of exciting projects aimed at understanding key questions in cancer biology that could not be addressed by purely genetic or biochemical approaches alone. Examples of these projects include:

• identification of the cellular substrates of matrix metalloproteases involved in metastasis;

• identification of the direct substrates of oncogenic forms of the epidermal growth factor receptor (EGFR);

• development of new, highly specific inhibitors of disregulated protein kinases such as EGFR; and

• development of new estrogen congeners for treatment of prostate cancer with little or no cardiac toxicity.