Treatment of lung cancer

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DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer death in the United States. The candidate has devoted to clinical and translational research of lung cancer with the hope of improving outcomes for this devastating disease. An area of accomplishment is in the treatment with chemoradiotherapy for poor-risk patients with lung cancer. Another area of expertise of the investigator is in capitalizing the radiosensitizing and antiangiogenic properties of taxol for improving chemoradiotherapy of non-small-cell lung cancer (NSCLC). The candidate was the first researcher to report the in vivo antiangiogenic property of taxol. Clinical trials have demonstrated the feasibility and efficacy of twice-weekly taxol and carboplatin with concurrent radiation for stage III NSCLC. In basic and translational research, the candidate has identified peptide ligands specific for surface receptors of lung cancer cells using the technology of combinatorial chemistry and cell-growth-on-bead assay. A pilot study is being supported by a R21 grant to test the feasibility of using these peptides to capture cancer cells from malignant pleural effusion. The candidate is applying for a K-24 award to support his endeavor of achieving the following aims: 1. To conduct a NCI-sponsored phase II trial in the California Cancer Consortium to test the tolerance and efficacy of tirapazamine in combination with the previously established regimen of twice-weekly taxol and carboplatin with concurrent radiation for stage III NSCLC. A correlative study will explore the feasibility of measuring plasma hypoxia-induced proteins, plasminogen activator inhibitor type I (PAl-l) and vascular endothelial growth factor (VEGF), in association with tumor response before and after chemoradiotherapy. 2. To further develop the peptide-bead technology as a high-yield and high-throughput clinical procedure for isolating and enriching lung cancer cells from pleural fluid. This technology may facilitate the diagnosis of lung cancer. 3. To identify novel peptide ligands specific for lung cancer. The long-term goal is to develop these peptide ligands as molecularly targeted therapy for lung cancer. 4. To recruit and train hematology and oncology specialists in clinical research of cancer therapy.