An additional potential benefit of the Champions Preclinical Platform is that it may be used to integrate prognostic testing with biomarker discovery. Biomarkers provide insight into the drug's mechanism of action and predict the specific tumor profile that an agent may be most effective in treating. Traditionally, biomarkers indicative of sensitivity to prospective chemo agents have been discovered in the late stages of drug development, resulting in exposure of clinical trial patients to toxic effects without benefit.

Biomerk Tumorgrafts provide a means to identify biomarkers at the early preclinical phase. If key biomarkers are discovered early, companion diagnostic tests may be developed to determine the chemotherapeutic agents that are most effective in treating the tumor. This enables the identification of patients that are most likely to benefit from specific drugs and the drugs most likely to be effective against specific tumor types.

To discover biomarkers, Biomerk Tumorgrafts are characterized through synergistic collaborations with diagnostic companies. The characterization methods include some or all of the following:

• Gene Expression
• Oncogene Mutations
• Comparative Genomic Hybridization (CGH)
• Promoter Methylation
• Micro-RNA
• Proteomics

Once characterized, the Tumorgrafts are tested with chemotherapeutic candidates. Biomarkers are discovered when selective tumor response occurs within a subset of the model Tumorgrafts. Testing patients' tumors for the presence of biomarkers assists in validating the predictive platform and applying the optimal treatment regimen.

Reference: Rubio-Viqueira B, Jimeno A, Cusatis G, et al. An in vivo platform for translational drug development in pancreatic cancer. Clin Cancer Res 2006; 12 (15) 4652-61.