This grant represents the first renewal of the UM EDRN Biomarker Development Lab (BDL) which was initiated 5 years ago. During this brief time period, our group has characterized a number of important prostate cancer biomarkers, the most noteworthy being the TMPRSS2-ETS gene fusions found in a majority of prostate cancers. This discovery led to first inaugural AACR Team Science Award in 2007. Looking forward, we propose extending our work in the discovery and refinement of biomarkers to facilitate the accurate diagnosis of prostate cancer using the TMPRSS2-ETS rearrangements as a foundation. We will also take on the significant mission of developing biomarkers to predict aggressive prostate cancer with the goal of distinguishing indolent from aggressive prostate cancer either prior to diagnosis or at the time of biopsy diagnosis. This study takes a systems biology approach to develop clinically relevant prostate cancer biomarkers for detection and risk assessment.
In Aim 1, we will extend work from the prior funding period to develop prostate cancer specific biomarkers to accurately diagnose prostate cancer and thus decrease unnecessary biopsies.
Aims 2 and 3 focus on the important clinical need to develop biomarkers to distinguish significant from insignificant disease.
Aim 2 will use high grade cancer as a surrogate of aggressive disease and Aim 3 we will use two clinically developed risk assessment tools as a surrogate measure of aggressive disease. A biomarker for aggressive disease would impact screening detection and clinical management of prostate cancer. The primary platform technologies we will employ (and have credible expertise) include next generation transcriptome sequencing, Affymetrix SNP arrays, lllumina DASL, Luminex xMAP-based multiplex antigen panels and mass spectrometry based metabolomics. The development of prostate cancer biomarkers for accurate diagnosis and risk assessment are urgently needed as recognized by the EDRN. Our proposal is highly ambitious given the wide range of discovery platforms proposed. Our team approach also extends beyond our BDL and into the EDRN Clinical Validation Center (CVC) where both PIs of this application have played roles in the Michigan/Harvard/WCMC CVC collection of over 1800 samples on EDRN protocol. Finally, our group has actively participated in the EDRN biomarker community and anticipates continuing to work with other BDL and CVCs to facilitate the overall mission of the EDRN.

Public Health Relevance

Recent studies suggest that regardless of clinical treatment offered, most men with clinically localized prostate cancer at time of initial diagnosis do not die of their disease but from other causes. As the U.S. population ages, the number of prostate cancer cases will increase representing an important impact on our health care system. Taken together, we urgently need the next generation prostate cancer screening biomarkers that will have high specificity and be associated with clinically significant disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA111275-08
Application #
8320739
Study Section
Special Emphasis Panel (ZCA1-SRLB-C (M1))
Program Officer
Kagan, Jacob
Project Start
2004-09-20
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2012
Total Cost
$685,047
Indirect Cost
$144,572
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
Shukla, Shipra; Cyrta, Joanna; Murphy, Devan A et al. (2017) Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance. Cancer Cell 32:792-806.e7
Piyarathna, Danthasinghe Waduge Badrajee; Rajendiran, Thekkelnaycke M; Putluri, Vasanta et al. (2017) Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder. Eur Urol Focus :
Sailer, Verena; Schiffman, Marc H; Kossai, Myriam et al. (2017) Bone biopsy protocol for advanced prostate cancer in the era of precision medicine. Cancer :
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
Pauli, Chantal; Hopkins, Benjamin D; Prandi, Davide et al. (2017) Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine. Cancer Discov 7:462-477
Shukla, Sudhanshu; Zhang, Xiang; Niknafs, Yashar S et al. (2016) Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer. Neoplasia 18:489-99
Rennert, Hanna; Eng, Kenneth; Zhang, Tuo et al. (2016) Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care. NPJ Genom Med 1:
Van Allen, Eliezer M; Robinson, Dan; Morrissey, Colm et al. (2016) A comparative assessment of clinical whole exome and transcriptome profiling across sequencing centers: implications for precision cancer medicine. Oncotarget 7:52888-52899
Mehra, Rohit; Vats, Pankaj; Cieslik, Marcin et al. (2016) Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney. Cancer Discov 6:1258-1266
Beltran, Himisha; Prandi, Davide; Mosquera, Juan Miguel et al. (2016) Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med 22:298-305

Showing the most recent 10 out of 151 publications