Since inception in 1995, the University of Michigan (U-M) Prostate SPORE has endeavored to tap the vast intellectual and physical resources of the U-M community to decrease the morbidity and mortality of prostate cancer (PCa). In this renewal application, U-M joins forces with Karmanos Cancer Institute (KCI) to propose a ?Michigan Prostate SPORE? leveraging our institutions' respective areas of strength. KCI has a non-overlapping patient population as U-M, which includes an underserved population. The Michigan 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 PCa. Successful translation of discoveries in the most recent grant period include: 1) The ETS gene fusions (which were discovered by this SPORE program) have been established as a urine test for the early detection of PCa (JAMA Oncology 2017 3:1085) and have been therapeutically targeted with peptidomimetic inhibitors (Cancer Cell 2017 31:844). 2) Our SPORE program played a significant role in defining the clinically actionable landscape of metastatic castration-resistant prostate cancer (mCRPC) (Cell 2015, 162:454) which led to the discovery that upwards of 20-25% of mCRPC harbor defects in DNA repair genes. As part of the TO-PARP study, we showed that mCRPC patients with DNA repair defects preferentially respond to PARP inhibitors (NEJM 2015, 373:1697). 3) Established that BET bromodomain inhibitors may be useful in the treatment of advanced PCa by blocking oncogenic transcription factor activity (Nature 2014, 510:278). 4) Several PCa-associated long non-coding RNAs, including PCAT1, Schlap1 (Nature Genetics 2013 45:1392), and ARlnc1 (Nature Genetics 2018, 50:814) were discovered and characterized. These bench-to-bedside applications were aided by horizontal collaborations with the University of Washington, Dana Farber, Memorial Sloan-Kettering, and Weill-Cornell Prostate SPOREs as well as the EDRN and vertical collaborations with SWOG and biotech companies. This application consists of four projects: Project 1: Targeting mCRPC Patients with Biallelic Loss of CDK12; Project 2: Integrating a Novel MiPS-Based Next- Generation Sequencing Urine Assay for the Early Detection of Unfavorable Risk PCa; Project 3: Exploring Ablation of the Androgen Receptor as a Therapeutic Approach for mCRPC; Project 4: Targeting Autophagy in the Treatment of mCRPC. These projects are complemented by strong, ongoing institutional commitments of money and space, successful Career Development and Developmental Research Programs, and three cores: Administration, Biostatistics/Bioinformatics, and Biospecimen/Pathology. The Michigan Prostate SPORE 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 from outside the PCa field, and utilizing flexibility to fund promising new research approaches. The interaction of our multidisciplinary group of investigators clearly makes the Michigan Prostate SPORE greater than the sum of its individual parts.

Public Health Relevance

The Michigan Prostate SPORE seeks to decrease the morbidity and mortality associated with prostate cancer by making scientific advances that address critical questions in prostate cancer tumorigenesis and treatment. In the Michigan Prostate SPORE renewal, four translational projects together identify and address major barriers and challenges that exist for the diagnosis and clinical management of prostate cancer and progression to metastatic disease. These projects are highly collaborative with respect to the multidisciplinary nature and expertise of the Co-Leaders.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA186786-07
Application #
10006863
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Arnold, Julia T
Project Start
2014-09-11
Project End
2024-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
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
Zhang, Yajia; Pitchiaya, Sethuramasundaram; Cie?lik, Marcin et al. (2018) Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression. Nat Genet 50:814-824
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 :
Niknafs, Yashar S; Pandian, Balaji; Gajjar, Tilak et al. (2018) MiPanda: A Resource for Analyzing and Visualizing Next-Generation Sequencing Transcriptomics Data. Neoplasia 20:1144-1149
Xiao, Lanbo; Tien, Jean C; Vo, Josh et al. (2018) Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer. Cancer Res 78:5731-5740
Piert, Morand; Shankar, Prasad R; Montgomery, Jeffrey et al. (2018) Accuracy of tumor segmentation from multi-parametric prostate MRI and 18F-choline PET/CT for focal prostate cancer therapy applications. EJNMMI Res 8:23
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
Rice, John D; Tsodikov, Alex (2017) Semiparametric profile likelihood estimation for continuous outcomes with excess zeros in a random-threshold damage-resistance model. Stat Med 36:1924-1935
Shen, Rex; Luo, Lan; Jiang, Hui (2017) Identification of gene pairs through penalized regression subject to constraints. BMC Bioinformatics 18:466

Showing the most recent 10 out of 65 publications