Specific Biomarkers in Bladder Cancer Prevention

膀胱癌在美国和全世界是一个严重的健康问题。据估计，仅在美国今年就将确诊56,500例。患膀胱癌的最高风险群体之一是前吸烟者。与不吸烟者相比，吸烟者患膀胱癌的风险增加了四倍多。前吸烟者发展膀胱癌的高风险和在这些个体中观察膀胱癌之前通常经过的延长的时间段使他们适合于使用可以早期检测疾病的标记物以及在那些被鉴定为早期疾病的人中应用化学预防剂。我们建议应用一种生物标志物，在膀胱癌发展的早期阶段特异性和敏感性地检测膀胱癌，然后将化学预防剂集中在这些人身上，而不是将化学预防剂作为第一疗程治疗所有吸烟者。如果这些研究证明是成功的，那么这些化学预防方法可以应用于使用标记物BLCA-4作为有效性措施的大量前吸烟者。 当膀胱癌被早期发现时，五年生存率约为94%，而疾病已经扩散的患者的生存率显着降低。 这里提出的假设是，尿液中BLCA-4的水平可以作为替代生物标志物，以评估膀胱癌动物模型中的化学预防剂。为了解决这一假设，我们提出以下具体目标： 1.利用代表既往吸烟者的疾病动物模型，检查BLCA-4表达在膀胱癌发展中的时间进程。 2.确定BLCA-4作为膀胱癌替代标志物的效用，从而允许快速评价化学预防化合物。 3.在初步研究中测试BLCA-4作为生物标志物的用途，在肉眼病变发展之前的早期阶段检测前吸烟者的膀胱癌，从而使其成为膀胱内和全身化学预防治疗的候选者。

DESCRIPTION (provided by applicant) Bladder cancer is a significant health problem in the United States and throughout the world. An estimated 56,500 cases will be diagnosed this year in the U.S. alone. One of the highest risk groups for developing bladder cancer is former smokers. Smokers have more than a four-fold increased risk for developing bladder cancer as compared with non-smokers. The high risk of former smokers for developing bladder cancer and the extended period of time which typically elapses prior to the observation of bladder cancer in these individuals make them appropriate for following with markers that can detect the disease early as well as the application of chemopreventive agents in those identified with early disease. Instead of treating all smokers with chemopreventive agents as a first course, we are proposing to apply a biomarker which appears to specifically and sensitively detect bladder cancer at an early stage in its development and then focus the chemopreventive agents on these individuals. If these studies prove successful, these chemopreventive approaches can then be applied to the large population of former smokers using the marker, BLCA-4, as a measure of effectiveness. When bladder cancer is detected early, the five-year survival rate is approximately 94% while patients with disease that has spread, have significantly lower survival rates. The hypothesis being addressed here is that urine levels of BLCA-4 can serve as a surrogate biomarker to evaluate chemopreventive agents in an animal model of bladder cancer. To address this hypothesis we propose the following specific aims: 1. To examine the time course of BLCA-4 expression in the development of bladder cancer utilizing an animal model of the disease representing former smokers. 2. To determine the utility of BLCA-4 as a surrogate marker of bladder cancer permitting the rapid evaluation of chemopreventive compounds. 3. To test in a pilot study, the use of BLCA-4 as a biomarker with which to detect bladder cancer in former smokers at an early stage, prior to the development of gross lesions and therefore making them candidates for chemopreventive therapies both intravesically as well as systemic.