A New Preclinical Paradigm for Pancreas Cancer

Abstract

Pancreas cancer confounds patient and physician alike. With an almost identical annual incidence and mortality, the disease has heretofore thwarted attempts to cure and even contain it. The approach to the patient with pancreas cancer is the same as for any cancer: detect it early, diagnose it accurately and eradicate it through a combination of surgery and chemical and radiotherapies. However, cancer of this organ eludes early detection, runs the risk of significant collateral injury when attempting to biopsy it for diagnosis, and resists all current forms of conventional chemotherapy and radiation. Moreover, the disease is as difficult to study in patients as it is to treat. Although classical experimental model systems have yielded significant information on genetic mutations of interest, they have not proved as useful in screening for drugs likely to be effective in patients. Mammalian model systems that faithfully mimic the full spectrum of the human disease from inception to invasion are needed. This chapter describes an integrated translational approach to developing and testing early detection, molecular diagnostic, chemopreventive and therapeutic strategies using state-of-the-art genetically engineered mouse models.