PCa is the leading cause of cancer-related deaths in American men. Androgen deprivation therapies (ADT) that target and suppress androgen receptor (AR) are the mainstay treatment of advanced prostate cancer. A majority of PCa initially responds well to ADT and is called androgen-dependent prostate cancer (ADPC). However, nearly all PCa treated with ADT become resistant to this treatment over a period of months or years, resulting in castration- resistant prostate cancer (CRPC), a lethal disease. Understanding the molecular events regulating AR transcriptional activities and driving CRPC progression is essential for the development of novel therapeutics to eradicate CRPC. The goal of the applicant is to utilize genomic and bioinformatics approaches to integrate big data to identify the key factors leading to drug resistance in prostate cancer. This will entail providing bioinformatics and integrative genomics analysis to various projects studying genetic and epigenetic regulations of AR cistrome and AR-mediated transcriptional program in the context of CRPC. In addition, Bigger Data will be collected either from public domains or generated internally with various collaborators and will be analyzed through integrative genomics coupled with network modeling to discover the driver events to castration-resistant prostate cancer.

Public Health Relevance

Prostate cancer is a leading cause of cancer-related death in American men with lethality due largely to castration-resistant prostate cancer (CRPC). This research project will use integrative genomics and bioinformatics analysis of Big Data to model key molecular events driving CRPC progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Project #
1R50CA211271-01
Application #
9221088
Study Section
Special Emphasis Panel (ZCA1-SRB-1 (A1))
Program Officer
Ault, Grace S
Project Start
2016-09-21
Project End
2021-08-31
Budget Start
2016-09-21
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$139,047
Indirect Cost
$50,199
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Fong, Ka-Wing; Zhao, Jonathan C; Song, Bing et al. (2018) TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression. Nat Commun 9:5007
Zhu, Sen; Zhao, Dongyu; Yan, Lin et al. (2018) BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nat Commun 9:500
Fong, Ka-Wing; Zhao, Jonathan C; Kim, Jung et al. (2017) Polycomb-Mediated Disruption of an Androgen Receptor Feedback Loop Drives Castration-Resistant Prostate Cancer. Cancer Res 77:412-422
Njoroge, Rose N; Unno, Kenji; Zhao, Jonathan C et al. (2017) Organoids model distinct Vitamin E effects at different stages of prostate cancer evolution. Sci Rep 7:16285
Putzbach, William; Gao, Quan Q; Patel, Monal et al. (2017) Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism. Elife 6:
Kim, J; Jin, H; Zhao, J C et al. (2017) FOXA1 inhibits prostate cancer neuroendocrine differentiation. Oncogene 36:4072-4080