 Biomarkers to better understand the mechanisms of action, primary and acquired resistance, and toxicity of these agents are urgently needed. The topic has been extensively reviewed and is considered a priority by the NCI. The need for such biomarkers is critical given the increasing number of permutations of targeted therapeutics and the need for biomarkers to guide patient and treatment selection both in clinical trials and in general use of anti-cancer therapy. Assay optimization and defining expected values of each marker or panel of markers is critical before use of such assays in large therapeutic clinical trials designed to target specific patient populations. In addition, understanding the biology and regulation of biomarkers related to tumor growth and tumor angiogenesis is also important. Most candidate biomarkers are themselves cellular growth factors, and are involved in not only tumor promotion and growth, but also in normal growth and development and in normal and abnormal tissues responses to injury. The primary purpose of the proposed project is to help refine new biomarkers and new and evolving technologies to assess them. 