DNA BASED METHODS TO DETECT BLADDER CANCER RECURRENCE

Traditional morphologic and cytologic methods, which are expensive and uncomfortable, fail to detect a sizable portion of bladder cancer cases or recurrences early enough to impact significantly upon patient survival. Molecular methods to detect genomic instability are beginning to play an increasing role in determining the critical genetic changes associated with transitional cell carcinoma (TCC) of the bladder. The analysis of genomic instability, caused by loss of heterozygosity or microsatellite alterations, is a powerful new and sensitive technique. This Phase I study is designed to establish the merit and feasibility of using the DNA-based approach to detect genomic instability and identify early or recurrent bladder cancer in exfoliated cells. We will analyze PCR-amplified DNA from paired (blood and urine) samples. Twenty markers, which can detect 95% of all primary bladder cancers, will be utilized to determine the presence of either microsatellite instability of loss of heterozygosity. Our long-range goal is to further develop and improve the molecular staging assay to increase throughput and cost-effectiveness. This sensitive assay has enormous potential as a rapid, low-cost, safe screening tool for early and recurrent bladder cancer. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 171 --PROJECT NUMBER......1 R43 CA74641-01 INVESTIGATOR NAME/ADDRESS FY 97 BOYNTON, ALTON L IRG/INTRAMURAL UNIT..ZRG2 NORTHWEST BIOTHERAPEUTICS LLC AWARD AMOUNT......... $100,000 120 NORTHGATE PLAZA, SUITE 236 SEATTLE, WA 98125 PERFORMING ORGANIZATION: NORTHWEST BIOTHERAPEUTICS, LLC TITLE URINE BASED MOLECULAR TEST FOR PROSTATE CANCER ABSTRACT: The long term goals of this project ar to: 1) develop a sensitive and accurate diagnostic urine test for prostate cancer; and, 2) create a "prostate profile" identifying prognostic subgroups of prostate cancer based on expression of molecular markers. We detected in urine sample the expression of specific genetic markers which appear in men with prostate cancer. This Phase I application will determine the feasibility of utilizing this test as a diagnostic and/or prognostic indicator in prostate cancer. We will initially optimize the collection of urine specimens with respect to cellular viability and RNA quality and quantity. Next, we will evaluate at least 100 additional urine specimens for specific gene expressions and, finally evaluate the relationship of laboratory data and clinical data for interpretation and validation of the prostate profile as a diagnostic screening test.