Cellular Mechanisms Underlying Pulmonary Stresses in Small Cell Lung Cancer

Small cell lung carcinoma accounts for about twenty percents of all lung cancers and kills approximately thirty thousands patients in this country every year. It is well documented that patients with primary small cell lung cancer suffer from persistent cough, dyspnea and lingering chest pain. These pulmonary stresses are debilitating and severely impair the quality of life of these patients. The long-term goals of this research project are to uncover the mechanisms underlying these symptoms, to delay the deteriorating process of the disease, and to develop new therapeutic strategies for alleviating these symptoms. One of the characteristic features of these cancer cells is their ability to secret a variety of chemical substances, and many of these substances have distinct biological activities. The working hypothesis of this proposal is that the gastrin-releasing peptide, a major type of these chemical substances, stimulates a specific group of sensory nerves in the lungs that are particularly sensitive to chemical irritants. It is well documented that these nerves, when activated, not only can cause chest pain, dyspnea and cough, but also release certain neurochemicals that can in tum promote the tumor growth. Therefore, such an interaction between these sensory nerves and cancer cells in the lungs may playa critical part in the deteriorating process of the disease, in addition to generating the debilitating symptoms in these patients. The main objective of this study is to uncover the mechanism underlying the action of the gastrin releasing peptide on the sensory nerves in the lung. We will isolate and culture the cells of these sensory nerves in the lungs from experimental animals (rats), and then expose the nerve cells to the gastrin-releasing peptide. Data obtained from our pilot experiment have already demonstrated the feasibility and potential significance of the proposed study. We believe that the results obtained from this study will improve our understanding of the pathogenic role of this interaction between these sensory nerves and the cancer cells. Further, the new information should also help to develop new therapeutic strategies for reducing the respiratory stresses in patients suffered from this type of lung cancer and to improve their quality of life.