PROSPECT: Profiling of Resistance Patterns Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

摘要

We will develop a high throughput therapeutic-target focused (TTF) profiling platform and will combine this with tumor genome wide mRNA profiling and with serum or plasma profiling of phosphopeptides and DNA. We will use these molecular profiles to help define how various molecular factors alone and in combination relate to resistance to therapy, to prognosis, and to metastatic patterns at relapse. Using tumor and blood samples from non-small cell lung cancer (NSCLC) patients as well as NSCLC cell lines with defined chemotherapy resistance patterns, we will examine how molecular profiles may confer resistance and will identify new, potential therapeutic targets. The PROSPECT approach will be novel in that we will assess tumors from NSCLC patients undergoing surgical resection after having received neoadjuvant therapy as a model of resistance. Tumor surviving neoadjuvant therapy would be expected to be enriched for resistant cells. We will define what combinations of targeted therapies are most effective against resistant cell lines with similar molecular profiles, and this will drive later clinical trials (beyond the scope of this Program).