SPORE in Prostate Cancer

简介（由申请人提供）：自1995年成立以来，密歇根大学（UIVI）前列腺孢子一直致力于利用密歇根大学社区庞大的智力和体力资源来降低前列腺癌（PCa）的发病率和死亡率。UIVI前列腺孢子支持一个由基础和临床研究人员组成的互动式小组进行转化研究项目，该项目在前列腺癌的诊断、预防和治疗方面取得了重大发现。在最近的资助期内，成功翻译的发现包括：1)开发了一种前列腺癌尿液检测方法，现在在CLIA参考实验室提供（Sci TransI Med. 2011）；2) ETS基因融合驱动的PCa对PARP抑制剂治疗敏感（Cancer Cell 2011），该研究启动了一项随机II期试验（NCTOI576172）；3) hoxb13基因的种系突变可增加患PCa的风险（N Engl J Med. 2012）。这是一种评估前列腺癌风险的测试；4)首次描述转移性去势抵抗性前列腺癌（CRPC）突变景观的研究（Nature 2012,）；5) Cabozantinib对前列腺癌骨转移患者有疗效，可减轻骨痛（J clinoncol . 2013）。通过与达纳法伯、贝勒、梅奥诊所和约翰霍普金斯前列腺孢子研究所以及EDRN的横向合作，以及与SWOG和生物技术公司的纵向合作，这些从实验室到床边的应用得到了帮助。本项目由四个多学科项目组成：项目1：精确医学方法阐明晚期前列腺癌进展和耐药机制；项目2:CRPC对卡博赞替尼的敏感和耐药机制；项目3：新型BET溴域抑制剂治疗晚期前列腺癌的研究；项目4:IncRNAs在尿液中作为PCa生物标志物的研究。这些项目是由正在进行的，成功的职业发展和发展研究计划补充。这些项目和计划得到了强有力的持续机构承诺的资金和空间支持，以及三个核心：行政管理、生物统计学和组织/信息学。UM前列腺孢子项目继续对其转化研究项目进行严格的科学审查，对基础和临床研究人员进行配对，从前列腺癌领域内外吸取科学家的专业知识，并利用灵活性资助有前途的新研究方法。我们的多学科研究小组的相互作用显然使前列腺孢子项目在UMCCC大于其单个部分的总和。

DESCRIPTION (provided by applicant): Since inception in 1995, the University of Michigan (UIVI) Prostate SPORE has endeavored to tap the vast intellectual and physical resources of the UM community to decrease the morbidity and mortality of prostate cancer (PCa). The UIVI Prostate SPORE supports an interactive group of basic and clinical investigators in a translational research program that has led to major discoveries in the diagnosis, prevention and treatment of prostate cancer. Successful translation of discoveries in the most recent grant period include: 1) development of a urine test for prostate cancer which is now offered in CLIA reference laboratories (Sci TransI Med. 2011); 2) ETS gene fusion driven PCa that are susceptible to PARP inhibitor therapy (Cancer Cell 2011) which initiated a randomized Phase II trial (NCTOI576172); 3) germline mutations in HOXB 13 gene that conferred increased risk for PCa (N Engl J Med. 2012). This is being developed as a test for assessing PCa risk; 4) the first study describing the mutational landscape of metastatic castrate resistant prostate cancer (CRPC) (Nature 2012,) and; 5) Cabozantinib was shown to have efficacy and decrease bone pain in prostate cancer patients with bone metastasis (J Clin Oncol. 2013). These bench-to-bedside applications were aided by horizontal collaborations with the Dana Farber, Baylor, Mayo Clinic and Johns Hopkins Prostate SPOREs as well as the EDRN and vertical collaborations with SWOG and biotech companies. This application consists of four multidisciplinary projects: Project 1: A Precision Medicine Approach to Elucidate Mechanisms of Progression and Resistance to Therapy in Advanced PCa; Project 2: Mechanisms of Sensitivity and Resistance to Cabozantinib in CRPC; Project 3: Development of Novel BET Bromodomain Inhibitors for the Treatment of Advanced PCa; Project 4: Development of IncRNAs as PCa Biomarkers in Urine. These projects are complemented by ongoing, successful Career Development and Developmental Research Programs. The projects and programs are supported by a strong ongoing institutional commitment of money and space as well as three cores: Administration, Biostatistics, and Tissue/Informatics. The UM Prostate SPORE program continues to place premiums on rigorous scientific review of its translational research programs, pairing of basic and clinical investigators, drawing on expertise of scientists from within and fro outside the prostate cancer field, and utilizing flexibility to fund promising new research approaches. The interaction of our multidisciplinary group of investigators clearly makes the Prostate SPORE program at the UMCCC is greater than the sum of its individual parts.