Clinical studies are ongoing to develop tissue lysate array conditions to quantify measures of the microenvironment in clinical samples. 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. These specimens will be obtained before and during treatment with small molecule kinase inhibitors. Application of CD31 to protein array technology is nearing completion with a cross validation using clinical samples impending. Application of the array technology to laboratory study of angiogenesis is in the planning stages. Studies with CAI are ongoing collaboratively, assessing the biological and biochemical results of its combination with COX2 inhibitors, inhibitors of receptor tyrosine kinases such as imatinib, and also with ECGC, the anti-oxidant component of green tea. Use of CAI for ophthalmologic disease has been licensed and a CRADA is also under development. CAI will be tested therapeutically for benefit in macular degeneration. 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 and will complement our continuing clinical work with signal transduction inhibition therapy.
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