APPROACH FOR COLON CANCER THERAPY USING APC PEPTIDES

该应用程序的广泛、长期目标是减少电流

The broad, long-term objective of this application is to reduce the current high morbidity and mortality from colorectal cancer (CRC) through improved treatment. The development of many colonic malignancies. This key event, mutation of the adenomatous polyposis coli (APC) gene, is associated with the development of most (80 percent) forms of sporadic CRC and is a early step in CRC tumorigenesis. APC mutation also causes familial adenomatous polyposis (FAP), a hereditary disease which carries a 100 percent risk for CRC in affected individuals. In FAP, APC mutation causes hyperproliferation of colonic crypt epithelial cells, presumably die to the inability of the mutant APC gene to suppress cell growth. Despite the strong evidence linking APC mutation and CRC, and indicating that APC suppresses growth of colonocytes in vivo and in vitro, the biochemical pathways through which APC modulates cellular functions are just beginning to be elucidated. Because APC appears to associate with specific cellular proteins, it has been postulated that it is through these interactions that APC inhibits cell growth. The application, which is directed at reactivating APC's growth-suppressing mechanism and ultimately reversing uncontrolled growth resulting from the effects of mutant APC in colorectal tumor cells, takes this postulate as a reasonable starting point. Accordingly, the specific aims are: 1) To further characterize APC's interaction with other cellular proteins, 2) To discover agents that mimic APC's functions, and 3) To tests these agents for tumor-growth suppressor activity using cells containing APC mutations. This will involve cell lines from FAP patients that have been established in an ongoing clinical genetic study designed to evaluate phenotypic manifestations, maintain clinical and family histories, identify and treat affected individuals, and determine the APC genotype. This study should provide an opportunity to translate research on the genetic etiology of colon cancer toward new approaches for cancer treatment through development of agents which mimic APC function and which thereby have potential to reverse the malignant cellular phenotype of the subset of cancers having APC inactivation.