PHARMACODYNAMIC ASSAYS FOR WNT/FRIZZLED AND HGF/C-MET SIGNALIN

Multiplexed assays for pharmacodynamic targets of high priority for the NCI will be developed using Meso Scale Diagnostics' (MSD) Multi-Array technology to facilitate multiple integrated pharmacodynamic readouts from a single tumor biopsy or surrogate tissue specimen. These assays will be suitable for measurement of molecular-level responses to treatment in conjunction with preclinical development of therapeutic agents. Assays will be developed to evaluate the Wnt/Frizzled and HGF/c-Met signaling pathways implicated in many malignancies, including renal cell carcinoma (RCC). These assays will be demonstrated in pre-clinical models, characterized cell lines, tumor xenograft tissues, and patient plasma samples. Optimized assays will be applied to patient samples in subsequent Phase 2 work, in collaboration with the NCI. Pre-clinical samples will be from commercial vendors or provided by our collaborators, Drs. Mier and Panka (Harvard University) from ongoing studies on treatment effects in cancer. MSD's multiplex capability (including measuring total and phosphorylated signaling proteins), exquisite assay sensitivity, minimal sample requirement, wide dynamic ranges, and ease of assay scalability, make this technology ideally suited to achieving the NCI's objectives for molecular pharmacodynamic applications. This research will provide valuable tools to evaluate and validate new anti-cancer agents in clinical trials and for eventual clinical use to monitor treatment.