METABOLISM OF AUTOCRINE PEPTIDES--SMALL CELL LUNG CANCER

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Small cell lung cancer (i.e. small oat-cell carcinoma) accounts for approximately 25% of all identifiable human lung cancers. This malignant neoplasm has a rapid growth rate and shows a propensity to metastasize and grow rapidly. In Arizona alone, there are 2,400 new cases of lung cancer diagnosed each year. Of these 2,400 cases, 600 are new cases of small cell lung cancer (SCLC). This proposal is designed to study and develop potential inhibitors of small cell lung cancer growth by inhibiting the formation of certain peptide hormones produced by the SCLC cells. These peptide hormones are known to affect SCLC by increasing its potential for abnormal growth. The hypothesis that we will test is that SCLC produces metabolic "byproduct" peptide hormones by proteolytic metabolism of larger "parent" proteins, and that these peptides cause SCLC to grow. If we can control the production of these peptide hormones by inhibiting the enzymes responsible for their formation, then we may be able to control SCLC growth. Our research approach can be seen as attempting to disrupt a cascade of events responsible for SCLC growth by altering the formation of the necessary catalysts (peptides) responsible for many of the symptoms of the disease. Our long term objective is to develop a drug (peptidase inhibitor) capable of acting on peptides produced from SCLC. In this way we will be controlling the growth of SCLC, and also controlling the formation of peptide hormones which have serious and deleterious side effects due to their hypersecretion from SCLC cells.