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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA085859-09
Application #
8303434
Study Section
Special Emphasis Panel (ZCA1-RPRB-O (M1))
Program Officer
Mohla, Suresh
Project Start
2000-04-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
9
Fiscal Year
2012
Total Cost
$2,080,291
Indirect Cost
$478,257
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Faltermeier, Claire M; Drake, Justin M; Clark, Peter M et al. (2016) Functional screen identifies kinases driving prostate cancer visceral and bone metastasis. Proc Natl Acad Sci U S A 113:E172-81
Morrissey, Colm; Vessella, Robert L; Lange, Paul H et al. (2016) The biology and clinical implications of prostate cancer dormancy and metastasis. J Mol Med (Berl) 94:259-65
Kumar, Akash; Coleman, Ilsa; Morrissey, Colm et al. (2016) Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Nat Med 22:369-78
Haider, Maahum; Zhang, Xiaotun; Coleman, Ilsa et al. (2016) Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases. Clin Exp Metastasis 33:239-48
Wu, Yu; Schoenborn, Jamie R; Morrissey, Colm et al. (2016) High-Resolution Genomic Profiling of Disseminated Tumor Cells in Prostate Cancer. J Mol Diagn 18:131-43
Henzler, Christine; Li, Yingming; Yang, Rendong et al. (2016) Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer. Nat Commun 7:13668
Brocqueville, Guillaume; Chmelar, Renee S; Bauderlique-Le Roy, Hélène et al. (2016) s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells. Oncotarget 7:29228-44
Qu, Xiaoyu; Jeldres, Claudio; Glaskova, Lena et al. (2016) Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence. J Mol Diagn 18:215-24
Yu, Shu-Han; Zheng, Qizhi; Esopi, David et al. (2015) A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells. Cancer Immunol Res 3:1175-84
Liu, Gang; Sprenger, Cynthia; Wu, Pin-Jou et al. (2015) MED1 mediates androgen receptor splice variant induced gene expression in the absence of ligand. Oncotarget 6:288-304

Showing the most recent 10 out of 149 publications