One strategy has been proposed for use in the Nf1 GEM models community, which involves the evaluation of new therapies in multiple mouse strains. New drugs would be rapidly screened using MPNST and leukemia GEM models for efficacy (therapeutic index), target validation, and potential “off-target” effects. These GEM models would be utilized for initial evaluation, based on the rapid growth of the tumors and the relative ease of measuring tumor growth. Drugs that exhibit activity in these models would be further analyzed in detailed PK/PD studies in other tumor models, such as orthotopic tumor explant models and transgenic mice harboring specific deregulated cancer-associated molecules or pathways. Optic glioma and neurofibroma (plexiform neurofibroma) GEM models may be better suited for chemoprevention studies as well as investigations of drugs that target specific cells in the tumor microenvironment (e.g., microglia and mast cells). Collectively, the combined use of each of the available robust preclinical GEM models would afford researchers the opportunity to comprehensively evaluate drugs prior to considering human clinical trials. Adapted with permission from a summary presentation by Susan Blaney, Cold Spring Harbor Laboratories, Banbury Center conference on “Barriers and Solutions in the Use of Mouse Models to Develop Therapeutic Strategies for Neurofibromatosis-Associated Tumors,” November 3–5, 2005.