ABSTRACT

Most human disease, as defined in clinical pathology, should be regarded as multifactorial, and its complexity must be understood at the molecular level. It has been recognized that all complex diseases, such as cancer, must be characterized in terms of the host organism [99]. Disease models will continue to play a significant role in modern drug discovery. Rapid genomic and proteomic discovery technologies reveal great insight into the disease phenotype at the gene and protein level. This increasing knowledge can be applied to a more mechanistically based and target-driven discovery process. In preclinical development, more emphasis will be based on a refined molecular characterization of the target rather than classical efficacy assessments in animal models. Proteins represent the main biological effector molecules of any given cell and appear most suitable for the target evaluation process. Classical proteomic approaches offer the unique opportunity to identify disease-specific changes in protein expression profile in a complex system comprising up to 10,000 proteins. This strategy will generate an increasing number of disease-specific protein markers that can be utilized for the evaluation of preclinical models.