This is a competitive renewal application for CA57179, a grant that was funded for the past 4 years and three months as the result of an RFA related to prostate cancer (PCA). Currently, this grant supports a collaborative effort among faculty interested in cytogenetics, molecular biology, pathology, and urology. The renewal application represents a continued pursuit of selected previous goals. The focus of this study is the use of PCA tissues derived from surgery (a) to attempt to define the factors that control the growth of PCAs and may cause the marked differences in aggressiveness observed in different patients and (b) to use the information derived from these studies and from other laboratories to devise conditions that will permit us to grow PCAs from tissues resected from most PCA patients. Until recently, most PCA work in research laboratories has relied on three cell lines: PC-3, DU 145, and LNCaP. Two of these lines, PC-3 and DU 145, lack evidence of functioning androgen receptors and fail to make prostate specific antigen, quantitatively the most abundant protein product of prostatic epithelial cells. While a few other models of PCA have been developed, they are (a) not generally available and (b) still very limited in their reflection of the broad spectrum of disease seen in PCA. Little is understood about the control of growth in PCA. The usually lengthy (5-20 years) survival of patients with PCA makes PCA a disease in which the ability to grow the tumors of individual patients might have unusual long-term translational significance. If we are able to achieve our goals, this approach might make it possible to develop knowledge of specific patients tumors that would facilitate a more specifically targeted approach to gene therapy, therapy directed against specific tyrosine kinases, antineoplastic chemotherapy, and immunotherapy. The long survival of these patients might allow one to refine these approaches to specific tumors before patients experience the protracted and severe bone pain that afflicts the majority of patients whose deaths are caused by prostate cancer.
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