Specific Biomarkers in Bladder Cancer Prevention

膀胱癌是美国乃至全世界的一个重大健康问题。据估计，今年仅在美国就将诊断出56,500例病例。前吸烟者是患膀胱癌风险最高的人群之一。与不吸烟者相比，吸烟者患膀胱癌的风险增加了四倍多。前吸烟者患膀胱癌的风险很高，而且在这些人身上观察到膀胱癌之前通常要经过很长一段时间，这使得他们适合使用可以早期检测到疾病的标志物进行跟踪，也适合在那些被确定为早期疾病的人身上应用化学预防药物。我们建议采用一种生物标志物，在膀胱癌发展的早期阶段特异性和敏感性地检测膀胱癌，然后将化学预防药物集中在这些个体上，而不是将化学预防药物作为第一疗程来治疗所有吸烟者。如果这些研究证明是成功的，那么这些化学预防方法就可以应用于大量的前吸烟者，使用标记物BLCA-4作为有效性的衡量标准。膀胱癌在早期发现时，5年生存率约为94%，而疾病已经扩散的患者生存率明显较低。

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.