In order to evaluate the microenvironment clinically, studies are ongoing to develop tissue lysate array conditions to assess angiogenic activity in microdissected tumor epithelium and stroma and for the application of these conditions to patient materials. Surrogate measurements of vascularity, such as stromal CD31 signals, and assessment of activation of receptor tyrosine kinase pathways and intracellular signaling nodal activity will be assessed in both tumor epithelium and stroma from the same biopsy specimens, before and during patient treatment with small molecule kinase inhibitors. Further collaborations are ongoing or under initiation to develop a nanochamber for CAI administration for local or ocular disease, to optimize new combination therapeutic approaches of CAI. The latter includes preclinical work in which CAI in combination with a cyclooxygenase-2 selective inhibitor results in supra-additive effects in a number of unrelated cell lines. Notably, this also results in conversion of the cytostatic effects of the two agents individually into cytotoxic activity of the combination. This is being modeled in a phase I clinical trial proposal. This comprehensive approach to angiogenesis and microenvironment study in the laboratory and patient samples will provide opportunity for proof of principle of molecularly targeted agents in stromal therapy.
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