SPORE in Prostate Cancer

描述（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UM社区的巨大智力和物质资源，以降低前列腺癌（PCa）的发病率和死亡率。UIVI Prostate SPORE支持基础和临床研究人员的互动小组进行转化研究计划，该计划在前列腺癌的诊断，预防和治疗方面取得了重大发现。在最近的资助期内，成功转化的发现包括：1）开发了一种前列腺癌的尿液检测方法，目前已在CLIA参考实验室提供（Sci TransI Med.2011）; 2）易受PARP抑制剂治疗影响的ETS基因融合驱动的PCa（Cancer Cell 2011），其启动了随机II期试验（NCTOI 576172）; 3）H 0XB 13基因中的生殖系突变，其赋予PCa风险增加（N Engl J Med.2012）。这被开发为用于评估PCa风险的测试; 4）描述转移性去势抵抗性前列腺癌（CRPC）的突变景观的第一项研究（Nature 2012），和5）卡博替尼显示出在具有骨转移的前列腺癌患者中具有功效并减少骨痛（J Clin Oncol. 2013年）。这些从实验室到床边的应用得到了与Dana Farber、Baylor、马约诊所和约翰霍普金斯前列腺孢子以及EDRN的横向合作以及与SWOG和生物技术公司的纵向合作的帮助。该申请由四个多学科项目组成：项目1：阐明晚期PCa进展和耐药机制的精准医学方法;项目2：CRPC对卡博替尼的敏感性和耐药性机制;项目3：开发用于治疗晚期PCa的新型BET溴结构域抑制剂;项目4：开发IncRNA作为尿液中PCa生物标志物。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的补充。这些项目和计划得到了资金和空间以及三个核心的强有力的持续机构承诺的支持：管理，生物统计学和组织/信息学。UM Prostate SPORE计划继续对其转化研究计划进行严格的科学审查，基础和临床研究人员配对，借鉴前列腺癌领域内外科学家的专业知识，并利用灵活性为有前途的新研究方法提供资金。我们的多学科研究小组的相互作用显然使UMCCC的前列腺孢子计划大于其各个部分的总和。

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.