EARLY DETECTION AND CHEMOPREVENTION OF BLADDER CANCER

University Of Texas Md Anderson Can Ctr, Houston TX

Investigators

Linked publications & trials

Abstract

Identification of early changes associated with the development of preneoplastic conditions, and especially those which are responsible for the progression to invasive cancer would provide important clues on early cancer development. It could also aid in the development of novel markers for early identification of occult neoplasia and monitoring chemopreventive treatment. We have chosen to take a whole genome approach to identifying up-regulated and down-regulated genes and to focus specifically on those that are important for development and progression of in situ preneoplastic conditions to invasive urinary bladder cancer. The core preliminary data for this proposal are the results of the application of our genome-wide model of urinary bladder cancer progression from occult in situ preneoplastic conditions to invasive cancer. In this approach the genome model will be complemented with proteomic and DNA microarray profiles of urinary bladder progression from intraurothelial precursor conditions to invasive disease. Such data will serve as a comprehensive database providing information on genetic and protein changes involved in the development and progression of one of the most common human cancers. Together with a strong translational component two major goals at the basic and clinical/translational level will be accomplished. First, a novel previously unknown set of genes and proteins will be identified using the emerging highly innovative genomic and proteomic technologies. These findings will provide important clues to understanding of molecular mechanism(s) of urinary bladder carcinogenesis. Secondly, we will validate the value of early detection using specific markers we have identified to the assessment of the efficacy of chemoprevention using unique large clinical data bases which include a prospective cohort of 200 patients with a prior history of superficial bladder TCC and an existing chemoprevention trial in which risk for recurrence and progression of bladder cancer is being evaluated in patients receiving Celecoxib. Since the transforming and tumor suppressor genes identified should be relevant to more than one cancer type, this data will have a significant impact on our understanding of multi-step carcinogenesis in general and will serve as a paradigm for the development of markers and diagnostic strategies for early detection and prevention of other types of cancer as well as bladder cancer.