ABSTRACT

This chapter analyzes the limitations of the nude mouse xenograft model for therapy studies. The deficiencies of the model should become the variables that define either more appropriate models or set the boundary conditions of the existing model. The optimism about the value of the model is based on the notion that treatment response obtained in panels of xenografts representing various tumor types is comparable to that in clinical practice. Tumor heterogeneity has become an accepted explanation for the failure of cancer therapy. Xenografts usually show a faster growth than patients' tumors, which can be attributed to an increase in growth fraction and/or a coinciding decrease in cell loss. Tumor blood flow is an important variable for oxygen supply, transport of nutrients, and drugs, and may thus influence response to therapy. A direct translation of therapy results from nude mouse to man should be carried out with precaution.