Edward A. Sausville

Mouse Models in Cancer Drug Discovery and Development

The basis for proceeding with development of an anticancer agent has historically resulted in part from the capacity of the agent to inhibit tumor cell proliferation either in tissue culture (in vitro) or in animals (in vivo), without specific reference to a molecular or cellular target of action. Indeed, the potentially useful effects of the vast majority of agents currently approved for use as safe and effective as oncologic therapeutics in humans were initially detected by their favorable performance in mouse models of human cancer. This chapter provides an overview of the types of mouse models used in cancer drug discovery and development, their strengths and limitations, how to interpret them, and caveats in the consideration of results from commonly used murine model studies. The algorithm currently in use at the National Cancer Institute (NCI) in the United States is presented. This chapter is meant to be a practical, working summary of practice rather than a comprehensive review of the topic. For the latter, the reader is encouraged to seek more encyclopedic treatments (1–3, among others).