Strategic importance of research support through pathology.

The pace at which new drug candidates are being identified by Discovery Research demands that they be screened for preclinical attributes rapidly and efficiently. The early identification and elimination of compounds with toxic liabilities will produce safer drugs in a shorter time period, and with an increased rate of success. Most major pharmaceutical companies now recognize the strategic role of pathology support for research and have developed specific units to effect this outcome. The early interaction of these pathologists with drug discovery teams to identify compounds with toxic liabilities is critical. Approaches being used include high throughput in vitro screens to predict the relative toxicity of discovery compounds and to provide early indications of underlying mechanisms, target profiling to predict consequences of receptor-ligand interactions at other-than-indicated target sites, and acute in vivo studies to establish tolerability limits and target organs of toxicity. These approaches include the application of contemporary tools such as genomics, proteomics, metabonomics, and genetically engineered animal models. To maximize the benefit of discovery pathology, it is critical that pharmaceutical companies also actively participate in non-proprietary knowledge sharing and the education of pathologists and toxicologists to lead these efforts in the future.