SPORE in Prostate Cancer

前列腺癌中的孢子

• 批准号: 7284852
• 负责人: PETER T SCARDINO
• 金额: $ 264.02万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-14 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284852
• 关键词: SPORE; Prostate; Cancer

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.

描述（由申请人提供）：前列腺癌中的MSKCC孢子，最初于2001年资助，重点介绍了四个广泛的转化研究目标：（1）为纳入验证的分子标记物的局部前列腺癌的预测预测模型更好，以改善治疗选择； （2）确定前列腺癌发生，进展和转移的关键分子和遗传机制； （3）为局部治疗后PSA升高的男性开发针对PSMA的DMA疫苗； （4）开发用于castrate抗性转移性癌症的新型药物。在孢子和我们的机构的大力支持下，我们取得了长足的进步。我们已经完成了一项长期研究，该研究在大型英国队列中等待，并将诊断活检标本作为标记分析的组织微阵列。我们创建了模仿人类疾病的十几个新的前列腺癌模型，并鉴定出和验证了预测性分子标记。我们已经记录了PSMA DNA疫苗在1期临床试验中的功效。我们已经证明，HSP90用Ansamycin靶向疗法会降解雄激素受体，并活跃于castrate转移性前列腺癌。现在，我们已经建立了一支经验丰富的，生产性的多学科研究人员团队，致力于前列腺癌的转化研究，这是一个大量的患者人群，可容纳参与临床试验，以及支持此类试验的高级基础设施。借助大量的科学家探索了前列腺癌的生物学并制定新的治疗策略，我们拥有健康的新想法的健康研究，以作为诊断和治疗性干预措施进行调查。在为下一个周期准备孢子时，我们保留了整体目标和四个主要的研究项目，这些项目起着灵活的，多学科的计划，我们能够将重点转移到新信息的原始目标框架内最有希望的研究领域。我们添加了一个新项目，即詹姆斯·艾莉森（James Allison）在这里被招募为免疫学主席的詹姆斯·艾莉森（James Allison）的免疫疗法的检查点封锁。我们将保留五个核心（生物测量，生物统计学，动物模型，动物成像和给药），并停止由MSKCC核心设施取代的DNA阵列核心。职业发展已成功地招募了四名新的翻译调查员到我们的孢子，发展研究为十名飞行员提供了超过180万美元的额外机构支持，其中一些获得了独立的资金。我们的研究人员与前列腺癌和机构中的其他孢子成功合作，他们是跨越孢子间临床试验和试点国家生物座席网络的领导者。在继续支持的情况下，MSKCC孢子良好，可以将新颖的诊断和治疗干预从实验室转移到人类疾病，目的是降低前列腺癌的发病率和死亡率。