SPORE in Prostate Cancer

描述(申请人提供)：前列腺癌是美国最常见的男性癌症之一，也是癌症发病率和死亡率的主要原因。在其整个历史中，约翰霍普金斯前列腺癌孢子公司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、预防和治疗方面的改进来降低前列腺癌的发病率和死亡率。这份竞争性续签提案包含六个新的翻译研究项目、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旨在引入一种全新的成像/治疗平台，其特征是使用肿瘤选择性启动子驱动的转基因；项目2希望提供治疗性嵌合RNA，其特征是适体介导与前列腺特异性膜抗原(PSMA)的选择性结合和针对DNA依赖的蛋白激酶的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治疗开始后的一小段时间内被取消的趋势作为疫苗免疫治疗的窗口；项目4提议跟进成功的合成致命功能基因组学筛选新的分子药物靶点，作为核苷类似DNA甲基转移酶抑制剂的合作伙伴，提供治疗组合用于晚期前列腺癌的临床试验；项目5要求骨髓间充质干细胞具有肿瘤特异性的归巢特性，以创建一个在前列腺癌细胞附近选择性输送和激活原毒素PRX302的平台；项目6，一项人口科学研究，测试测量基质细胞和癌细胞中端粒长度在预测前列腺癌死亡风险方面的应用。这些项目由一个行政核心、一个病理学/生物医学核心和一个生物统计/生物信息学核心提供支持。最后，职业发展和发展研究计划，加上帕特里克·C·沃尔什前列腺癌研究基金每年提供的100万美元，分别包括人力资本和创新想法的管道，这将推动未来的孢子发展。

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.