Since inception in 1995, the University of Michigan (UIVI) Prostate SPORE has endeavored to tap the vast intellectual and physical resources of the UM community to decrease the morbidity and mortality of prostate cancer (PCa). The UIVI Prostate SPORE supports an interactive group of basic and clinical investigators in a translational research program that has led to major discoveries in the diagnosis, prevention and treatment of prostate cancer. Successful translation of discoveries in the most recent grant period include: 1) development of a urine test for prostate cancer which is now offered in CLIA reference laboratories (Sci TransI Med. 2011);2) ETS gene fusion driven PCa that are susceptible to PARP inhibitor therapy (Cancer Cell 2011) which initiated a randomized Phase II trial (NCTOI576172);3) germline mutations in HOXB 13 gene that conferred increased risk for PCa (N Engl J Med. 2012). This is being developed as a test for assessing PCa risk;4) the first study describing the mutational landscape of metastatic castrate resistant prostate cancer (CRPC) (Nature 2012,) and;5) Cabozantinib was shown to have efficacy and decrease bone pain in prostate cancer patients with bone metastasis (J Clin Oncol. 2013). These bench-to-bedside applications were aided by horizontal collaborations with the Dana Farber, Baylor, Mayo Clinic and Johns Hopkins Prostate SPOREs as well as the EDRN and vertical collaborations with SWOG and biotech companies. This application consists of four multidisciplinary projects: Project 1: A Precision Medicine Approach to Elucidate Mechanisms of Progression and Resistance to Therapy in Advanced PCa;Project 2: Mechanisms of Sensitivity and Resistance to Cabozantinib in CRPC;Project 3: Development of Novel BET Bromodomain Inhibitors for the Treatment of Advanced PCa;Project 4: Development of IncRNAs as PCa Biomarkers in Urine. These projects are complemented by ongoing, successful Career Development and Developmental Research Programs. The projects and programs are supported by a strong ongoing institutional commitment of money and space as well as three cores: Administration, Biostatistics, and Tissue/Informatics. The UM Prostate SPORE program continues to place premiums on rigorous scientific review of its translational research programs, pairing of basic and clinical investigators, drawing on expertise of scientists from within and fro outside the prostate cancer field, and utilizing flexibility to fund promising new research approaches. The interaction of our multidisciplinary group of investigators clearly makes the Prostate SPORE program at the UMCCC is greater than the sum of its individual parts.

Public Health Relevance

The ultimate objective of the University of Michigan (UM) Prostate SPORE is to decrease the morbidity and mortality of prostate cancer. The UM Prostate SPORE will achieve this objective by continuing to define the molecular aberrations of prostate cancer, allowing the development of better diagnostic and prognostic tests as well as improve therapy for afflicted men.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA186786-01
Application #
8738942
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (M1))
Program Officer
Hruszkewycz, Andrew M
Project Start
2014-09-11
Project End
2019-08-31
Budget Start
2014-09-11
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$2,162,000
Indirect Cost
$768,021
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Hussain, Maha; Daignault-Newton, Stephanie; Twardowski, Przemyslaw W et al. (2018) Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012. J Clin Oncol 36:991-999
Salami, Simpa S; Hovelson, Daniel H; Kaplan, Jeremy B et al. (2018) Transcriptomic heterogeneity in multifocal prostate cancer. JCI Insight 3:
Zhao, Shanshan; Leonardson, Amy; Geybels, Milan S et al. (2018) A five-CpG DNA methylation score to predict metastatic-lethal outcomes in men treated with radical prostatectomy for localized prostate cancer. Prostate :
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Wu, Yi-Mi; Cie?lik, Marcin; Lonigro, Robert J et al. (2018) Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer. Cell 173:1770-1782.e14
Robinson, Dan R; Wu, Yi-Mi; Lonigro, Robert J et al. (2017) Integrative clinical genomics of metastatic cancer. Nature 548:297-303
Jin, Feng; Thaiparambil, Jose; Donepudi, Sri Ramya et al. (2017) Tobacco-Specific Carcinogens Induce Hypermethylation, DNA Adducts, and DNA Damage in Bladder Cancer. Cancer Prev Res (Phila) 10:588-597

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