SPORE in Prostate Cancer

描述（由申请人提供）：前列腺癌是美国男性最常见的癌症之一，也是癌症发病率和死亡率的主要原因。纵观其历史，约翰霍普金斯大学前列腺癌孢子一直致力于通过将新的实验室研究发现转化为前列腺癌筛查，检测，诊断，预防和治疗的改进来降低前列腺癌的发病率和死亡率。这项竞争性更新提案包含六个新的转化研究项目，三个核心资源，两个职业发展项目和两个发展研究项目。项目#1旨在引入一个全新的成像/治疗平台，其特点是使用肿瘤选择性启动子驱动的转基因；项目#2希望提供一种治疗性嵌合RNA，具有介导前列腺特异性膜抗原（PSMA）选择性结合的适体和针对dna依赖性蛋白激酶的siRNA，以选择性地增强前列腺癌细胞的放射敏感性；项目#3计划利用前列腺癌免疫耐受在雄激素剥夺疗法开始后的短时间内被废除的趋势，作为疫苗免疫疗法的一个窗口；项目#4建议对新分子药物靶点进行成功的合成致死功能基因组筛选，作为核苷类似物DNA甲基转移酶抑制剂的合作伙伴，为晚期前列腺癌的临床试验提供治疗组合；项目#5利用骨髓间充质干细胞的肿瘤特异性归巢特性，为前列腺癌细胞附近的原蛋白PRX302的选择性传递和激活创造了一个平台；6号项目是一项人口科学研究，它测试了在基质细胞和癌细胞中测量端粒长度在预测前列腺癌死亡风险方面的效用。这些项目由行政核心、病理学/生物标本核心和生物统计学/生物信息学核心提供支持。最后，职业发展和发展研究项目，由Patrick C. Walsh前列腺癌研究基金每年提供的100万美元补充，分别包括人力资本和创新理念的管道，这将推动《孢子》未来的发展。

DESCRIPTION (provided by applicant): Prostate cancer is one of the most commonly diagnosed cancers in men in the United States and a major cause of cancer morbidity and mortality. Throughout its history, the Johns Hopkins Prostate Cancer SPORE has focused on reducing prostate cancer incidence and mortality by translating new laboratory research discoveries into improvements in prostate cancer screening, detection, diagnosis, prevention, and treatment. This competitive renewal proposal contains six new Translational Research Projects, three Core Resources, two Career Development Projects, and two Developmental Research Projects. Project #1 aims to introduce an entirely new imaging/therapy platform featuring the use of tumor-selective promoter driven transgenes; Project #2 hopes to deliver a therapeutic chimeric RNA, featuring an aptamer mediating selective binding to prostate-specific membrane antigen (PSMA) and an siRNA against the DNA-dependent protein kinase, to selectively augment the radiosensitivity of prostate cancer cells; Project #3 plans to exploit the tendency for prostate cancer immune tolerance to become abrogated for a brief period of time following initiation of androgen deprivation therapy as a window for vaccine immunotherapy; Project #4 proposes to follow-up on a successful synthetic lethal functional genomics screen of new molecular drug targets as partners for nucleoside analog DNA methyltransferase inhibitors to deliver treatment combinations to clinical trials for advanced prostate cancer; Project #5 commandeers the tumor-specific homing properties of bone marrow derived mesenchymal stem cells to create a platform for selective delivery and activation of the protoxin PRX302 near prostate cancer cells; Project #6, a population science study, tests the utility of measured telomere lengths in stromal cells and cancer cells in predicting risk for prostate cancer death. These Projects are supported by an Administrative Core, a Pathology/Biospecimen Core, and a Biostatistics/Bioinformatics Core. Finally, the Career Development and Developmental Research Programs, supplemented by $1,000,000 annually from the Patrick C. Walsh Prostate Cancer Research Fund, comprise pipelines of human capital and innovative ideas, respectively, which will fuel future SPORE advances.