Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract: The invention provides improved methods for measuring enzymatic activities involved in the oxidative and non-oxidative pentose phosphate pathways, and other thiamine pyrophosphate containing enzymes, which are commonly elevated in tumor cells. The assays of the invention are useful for optimizing therapeutic dosing and scheduling of drugs acting on the pentose phosphate pathways by sampling and monitoring enzymatic levels in a treated patient over time. Finally, the assays are useful for identifying and characterizing compounds having beneficial therapeutic effects.