SPORE in Prostate Cancer

前列腺癌中的孢子

• 批准号: 7126965
• 负责人: PETER T SCARDINO
• 金额: $ 238.33万
• 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/7126965
• 关键词: antineoplastics; carcinogenesis; neoplasm /cancer therapy; prostate neoplasms

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.

MSKCC SPORE前列腺癌研究项目于2001年首次获得资助，主要关注四个广泛的转化研究目标：(1)开发更好的局部前列腺癌预后预测模型，结合经过验证的分子标记来改善治疗选择；(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)针对局部治疗后PSA升高的男性开发针对PSMA的DMA疫苗；(4)开发基于新机制的治疗去势耐药转移性癌症的药物。在《孢子》和我们的机构的大力支持下，我们取得了相当大的进步。我们已经在英国的一个大型队列中完成了一项长期的观察等待研究，并收集了诊断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种新的前列腺癌动物模型，模仿人类疾病，并确定和验证了预测性分子标记。我们已经在一期临床试验中证实了PSMA DNA疫苗的有效性。我们已经证明，用安霉素进行Hsp90靶向治疗可降解雄激素受体，对去势转移性前列腺癌有效。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研究，有大量的患者可以参与临床试验，并有一流的基础设施来支持这些试验。随着大量科学家探索前列腺癌的生物学和开发新的治疗策略，我们有一个健康的新想法管道，成熟的研究作为诊断和治疗干预措施。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，作为灵活的多学科项目，我们能够在原始目标的框架内，随着新信息的出现，将重点转移到最有前途的研究领域。我们增加了一个新项目，前列腺癌免疫治疗中的检查点阻断，由詹姆斯·艾利森（James Allison）主持，他最近被聘请为免疫学主席。我们将保留五个核心（生物标本、生物统计学、动物模型、动物成像和管理），并停止DNA阵列核心，取而代之的是MSKCC核心设施。Career Development已经成功地为我们的《孢子》招募了4名新的转化研究人员，Development Research已经为10个试点项目提供了超过180万美元的额外机构支持，其中一些已经获得了独立资金。我们的研究人员成功地与前列腺癌的其他孢子和机构合作，他们在孢子间临床试验和试点国家生物储存库网络中处于领先地位。在持续的支持下，MSKCC SPORE有能力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。