): Lung cancer is the leading cause of cancer related deaths among both males and females in the United States. Surgical resection remains the only curative therapy for patients with non-small cell lung cancer (NSCLC). Despite undergoing curative resection, a large percentage of patients (30 to 40%) with stage I (node-negative) NSCLC develop recurrent disease. Improvements in adjuvant therapy and in the ability to identify those patients most likely to benefit from adjuvant therapy are essential to improving survival in patients with NSCLC. The proposed study uses common molecular genetic events in the neoplastic progression of NSCLC to improve the ability to assign pathological stage, determine prognosis, and to detect disease recurrence in patients with early stage disease. The influence of p53 and K-ras gene mutations on disease-free and overall survival will be examined in patients with node-negative NSCLC. Molecular techniques will be used to determine the presence of micrometastatic disease in regional lymph nodes in patients undergoing surgical resection. The influence of micrometastatic disease on clinical outcome will be determined for patients with stage I NSCLC. In addition, tumor-specific p53 and K-ras gene mutations and/or microsatellite alterations will be identified in the serum DNA of patients with early-stage NSCLC and their presence correlated with clinical outcome. Completion of the research project will enable the candidate, an Assistant Professor in General Surgery with a strong interest in surgical oncology, to learn state-of-the-art molecular techniques with previously demonstrated clinical utility in the staging and screening of patients with cancer. The mentor's laboratory is an ideal place to pursue this project having made substantial contributions in this field. In addition, the wider network of investigators in the field of cancer genetics at the candidate's institution provides a constructive setting for critical review and support of ongoing research in this field. Completion of the proposed mentored training period will provide the candidate with an excellent foundation for pursuing his long-term goals in academic surgical oncology.
