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
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Tang, Xi; Mahajan, Sumit S; Nguyen, Liem T et al. (2014) Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis. Oncotarget 5:1352-62
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Thadani-Mulero, Maria; Portella, Luigi; Sun, Shihua et al. (2014) Androgen receptor splice variants determine taxane sensitivity in prostate cancer. Cancer Res 74:2270-82
Yu, X; Cates, J M; Morrissey, C et al. (2014) SOX2 expression in the developing, adult, as well as, diseased prostate. Prostate Cancer Prostatic Dis 17:301-9

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