Mechanisms and Markers of Prostate Cancer Metastases

描述(申请人提供)：在此续期重新提交，我们。建议继续研究前列腺癌(CAP)的转移，特别是关注CAP在骨中的扩散和生长。这项工作协调了华盛顿大学(UW)环境内各种来源之前的许多工作，是多学科的，包括癌症和骨生物学、癌症内分泌学、病理学和基因组学。机构合作伙伴包括弗雷德·哈钦森癌症研究中心和华盛顿大学干细胞科学研究所。对帽状骨转移机制的探讨很少，部分原因是缺乏合适的动物模型和标本。正如进度报告将证明的那样，我们的研究人员已在很大程度上克服了这些限制，所获得的资源将使我们能够实现所提出的科学目标。这个P01包括3个项目和2个核心。项目1题为“播散性肿瘤细胞的检测、分离和特征”。这个项目将对DTC的基因组特征进行描述，观察与进展和生物功能的相关性。它结合了多项研究，探索DTC的干细胞方面以及DTC在肿瘤休眠中的作用。这是一个新的项目，由Robert Vessella博士领导，取代了以前的项目1。项目2的标题是“跨膜蛋白水解酶与前列腺癌的发生”。这个由皮特·纳尔逊博士领导的项目将主要关注丝氨酸蛋白酶TMPRSS2和基因融合TMPRSS2-ERG。项目3的标题是：前列腺癌对1型胰岛素样生长因子抑制反应的决定因素。该项目由Steve Plymate博士领导，具有很高的翻译性，因为它专注于更好地了解IGF-1R的作用，因为华盛顿大学和其他地方正在进行针对该受体的临床试验。项目2和项目3是本供资期间非常成功的研究的延续。核心A是生物素核心，负责获取、加工和分配生物素。它还进行临床前异种移植研究，并为整个P01计划提供统计支持。核心B是向调查员提供全面行政支助的行政核心。

DESCRIPTION (provided by applicant): In this renewal resubmission, we. propose to continue studies on prostate cancer (CaP) metastasis, especially focusing on the dissemination and growth of CaP in bone. This effort has coordinated much previous work from a variety of sources within the University of Washington (UW) milieu and is multidisciplinary, incorporating cancer and bone biology, cancer endocrinology, pathology and genomics. Institutional partners include the Fred Hutchinson Cancer Research Center and the UW Institute of Stem Cell Sciences. Inquiries into the mechanisms of CaP bone metastasis, are poorly studied, in part because of a lack of appropriate animal models and specimens. As the Progress Reports will demonstrate, these limitations have been largely overcome by our investigators, and the derived resources will enable the pursuit of the scientific objectives proposed. This P01 consists of 3 projects and 2 cores. Project 1 is entitled "The Detection, Isolation and Characterization of Disseminated Tumor Cells". This project will genomically characterize the DTC, looking at correlates to progression and biological function. It incorporates multiple studies exploring the stem cell aspects of DTC and the role of DTC in tumor dormancy. This is a new project, led by Dr. Robert Vessella that replaces the previous Project 1. Project 2 is entitled "Transmembrane Proteases and Prostate Carcinogenesis". This project, led by Dr. Pete Nelson, will focus heavily on the serine protease TMPRSS2 and the gene fusion TMPRSS2-ERG. Project 3 is entitled: "Determinants of Response to Type 1 Insulin-like Growth Factor Inhibition in Prostate Cancer". This project is led by Dr. Steve Plymate and is highly translational as it is focused on better understanding the role of IGF-1R as clinical trials at UW and elsewhere are being conducted to target this receptor. Projects 2 and 3 are continuations of very successful studies during the current funding period. Core A is the Biospecimen Core which acquires processes and distributes biospecimens. It also conducts pre-clinical xenograft studies and provides statistical support to the overall P01 program. Core B is the Administrative Core which provides overall administrative support to the investigators.