BIOCHEMISTRY OF THE BOMBESIN-LIKE-PEPTIDE RECEPTOR

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Lung cancer is the leading cause of cancar deaths in the U.S. About 25% of cases are small cell lung carcinoma (SCLC), which, despite aggressive and toxic therapy, carries a less than 10% survival at five years. The ultimate goal of this project is to develop new therapeutic strategies for SCLC. SCLC cells secrete and contain a growth factor, bombesin, which stimulates their growth by interaction with a specific cell surface receptor. Disruption of this interaction should lead to cell death. This project proposes 1) to characterize the properties of and purify the receptor for this growth factor, bombesin; 2) to delineate the mechanism of signal transduction biochemically which results in cell proliferation; 3) to utilize the defined properties of the interaction between bombesin and its receptor, and the purified receptor itself, to develop new diagnostic and therapeutic approaches to the management of SCLC using monoclonal antibodies, toxin conjugates and ligand analogs.