PHARMACODYNAMIC ASSAYS FOR CANCER THERAPEUTICS

Pharmacodynamic assays that measure levels of cellular proteins of relevance to cancer will be developed using Meso Scale Diagnostics (MSD) MULTI-ARRAY technology. These assays will be suitable for ¿real time¿ preclinical and clinical sample testing, and should allow rapid evaluation of treatment, responses, gauge treatment correspondence to tumor stasis/regression, allow patient stratification for clinical trials and facilitate clinical validation of cancer therapeutics at early stages of drug development. Assays will be demonstrated in pre-clinical models, namely mouse xenographs of human solid tumors and molecularly characterized cancer cell lines representing different cancer subtypes. Optimized assays will be applied to patient tumor biopsies or surrogate tissues as appropriate, from patients before and after selected drug treatments where possible. The therapeutic agents used will primarily target the PI3k/Akt/mTOR and MAPK signaling pathways, and markers selected are relevant to these pathways. MSD¿s multiplex capability (including measuring total and phosphorylated forms of several targets, exquisite assay sensitivity, minimal sample requirement and wide dynamic ranges make this technology ideally suited to achieving the NCI¿s objectives for molecular pharmacodynamic applications.