Transplanted tumor models for preclinical drug testing and the potential benefit of genetically engineered mouse models

Abstract

Tumor models in rodents have historically served a key role in preclinical anticancer screening programs to evaluate biological activity and to optimize antitumor activity for new compounds. While the role of mouse tumor models in drug development programs has evolved and its predictive capabilities for humans continue to be debated, it is important to note that correlative drug responses have, and continue to demonstrate activity in preclinical mouse models for a majority of the clinically approved chemotherapeutic agents. However, the need for new technologies, strategies, and data analyses that provide greater efficiency in selecting compounds for development, and better predict clinical outcomes, cannot be overstated. Currently, it is predicted that approximately 1.5 million Americans will be diagnosed with cancer annually (American Cancer Society, Cancer facts and figures, 2008). Therefore, discovery of effective treatment strategies is paramount. Advances in the development of novel molecularly targeted agents, more effective use of traditional transplant models, and greater use of genetically engineered mice is expected to improve the accuracy of identifying therapeutic targets and effective compounds (alone or in combination) in the preclinical screening process. This will allow therapeutic agents to be more quickly and safely transitioned into human patients to improve their longevity and quality of life.