The development of therapeutic modalities for the treatment of human lung cancer has, to date, been disappointing. Classification of lung tumors with regard to their metabolic potential is particularly important for developing a systematic approach for the identification of active anti-lung tumor agents. We have, therefore, initiated this project in order to develop a relevant and feasible plan for classification of human lung tumors, as well as for identification of effective new lung cancer treatment modalities. This project will interface the clinical aspects of human lung cancer with basic science and applied science technologies which are currently available in an effort to provide a comprehensive program for characterization of lung tumors based on their morphological, ultrastructural, biochemical, metabolic, and molecular genetic characteristics as well as establish in vitro and in vivo techniques for investigating potential antitumor drugs against primary human lung tumors. The initial results from our laboratories document the feasibility and relevance of this project by demonstrating: (1) considerable variation in prostanoid and 4-ipomeanol metabolism as well as cytokeratin expression among individual fresh human lung tumor specimens as well as lung tumor cell lines, (2) the ability to establish and propagate primary lung tumor cell cultures which will provide material for in vitro drug screening, establishing long term tumor cell lines, and for comparative biochemical studies, (3) the ability to propagate human lung tumors in the lungs of nude mice by novel intrabronchial and intrathoracic implantation methods which allow for improved in vivo propagation, biochemical and drug screening studies. An ultimate goal of this project is to provide a paradigm for individualized lung cancer characterization and pharmacoselective drug treatment based on the biochemical profiles of individual lung tumors and corresponding normal lung tissue.
