SPORE in Prostate Cancer

描述(申请人提供)：前列腺癌中的MSKCC孢子项目，最初于2001年获得资助，专注于四个广泛的翻译研究目标：(1)结合经过验证的分子标记物以改进治疗选择，开发更好的局限性前列腺癌预后预测模型；(2)确定前列腺癌发生、发展和转移的关键分子和遗传学机制；(3)针对PSA局部治疗后PSA升高的男性开发以PSMA为靶向的DMA疫苗；以及(4)开发针对去势耐受转移癌症的新型基于机制的药物。在孢子和我们机构的大力支持下，我们取得了长足的进步。我们已经完成了一项在英国大型队列中观察等待的长期研究，并收集了诊断性活检标本作为组织微阵列进行标记分析。我们已经创建了十几个模仿人类疾病的前列腺癌新动物模型，并识别和验证了预测性分子标记。我们已经在一期临床试验中记录了PSMA DNA疫苗的有效性。我们已经证明，使用安沙霉素的HSP90靶向治疗可以降解雄激素受体，并对去势转移性前列腺癌起到积极的作用。我们现在拥有一支经验丰富、富有成效的多学科研究团队，致力于前列腺癌的转化性研究，拥有一大批愿意参与临床试验的患者，以及支持此类试验的一流基础设施。随着一大批科学家探索前列腺癌的生物学并开发新的治疗策略，我们有了一条健康的管道，作为诊断和治疗干预措施进行研究的新想法已经成熟。在为下一个周期准备我们的孢子时，我们保留了总体目标和四个主要研究项目，这些项目作为灵活的多学科计划，随着新信息的出现，我们能够将重点转移到原始目标框架内最有前途的研究领域。我们增加了一个新的项目，前列腺癌免疫治疗中的检查点封锁，由James Allison最近招募为免疫学主席。我们将保留五个核心(生物质谱学、生物统计学、动物模型、动物成像和管理)，并停止DNA阵列核心，由MSKCC核心设施取代。Career Development已经成功地向我们的孢子招募了四名新的翻译研究员，发展研究已经为十个飞行员提供了超过180万美元的额外机构支持，其中几个已经实现了独立资助。我们的研究人员成功地与前列腺癌和机构中的其他孢子合作，他们一直是孢子间临床试验和国家生物信息库网络试点的领导者之一。在持续的支持下，MSKCC孢子处于有利地位，可以将新的诊断和治疗干预措施迅速从实验室转移到人类疾病，目标是降低前列腺癌的发病率和死亡率。

DESCRIPTION (provided by applicant): The MSKCC SPORE in Prostate Cancer, initially funded in 2001, focused on four broad translational research goals: (1) to develop better predictive models of prognosis for localized prostate cancer incorporating validated molecular markers to improve treatment selection; (2) to identify critical molecular and genetic mechanisms of prostate carcinogenesis, progression, and metastasis; (3) to develop PSMA- targeted DMA vaccines for men with rising PSA after local therapy; and (4) to develop new mechanism- based drugs for castrate-resistant metastatic cancers. With strong support from the SPORE and our institution, we have made considerable progress. We have completed a long-term study of watchful waiting in a large British cohort and have collected diagnostic biopsy specimens as tissue microarrays for marker analyses. We have created more than a dozen new animal models of prostate cancer that mimic the human disease, and identified and validated predictive molecular markers. We have documented the efficacy of a PSMA DNA vaccine in a phase 1 clinical trial. And we have demonstrated that Hsp90 targeted therapy with ansamycin degrades the androgen receptor and is active against castrate metastatic prostate cancer. We now have in place an experienced, productive multidisciplinary team of investigators committed to translational research in prostate cancer, a large patient population amenable to participation in clinical trials, and superb infrastructure to support such trials. With a large cadre of scientists exploring the biology of prostate cancer and developing new therapeutic strategies, we have a healthy pipeline of new ideas ripe for investigation as diagnostic and therapeutic interventions. In preparing our SPORE for the next cycle, we have retained the overall objectives and the four major research projects, which function as flexible, multidisciplinary programs where we are able to shift emphasis to the most promising areas of research within the framework of original goals as new information emerges. We have added one new project, Checkpoint Blockade in Immunotherapy of Prostate Cancer, by James Allison, recently recruited here as Chair of Immunology. We will retain five cores (Biospecimen, Biostatistics, Animal Models, Animal Imaging, and Administration) and discontinue the DNA Array Core, replaced by the MSKCC core facility. Career Development has successfully recruited four new translational investigators to our SPORE, and Developmental Research has funded ten pilots with over $1.8 million in additional institutional support, several of which have achieved independent funding. Our investigators collaborate successfully with other SPOREs in Prostate Cancer and institutions and they have been among the leaders in inter-SPORE clinical trials and the pilot National Biorepository Network. With continued support the MSKCC SPORE is well positioned to move novel diagnostic and therapeutic interventions rapidly from the laboratory to the human disease with the goal of reducing morbidity and mortality from prostate cancer.