.. Currently available AR antagonists such as bicalutamide have limited activity in castration-resistant prostate cancer (CRPC). Mechanistic studies have shown that the bicalutamide liganded AR can accumulate in the nucleus and bind to chromatin, but that it does not effectively recruit coactivator proteins and instead can recruit the corepressor proteins NCoR and SMRT. This ability to mediate chromatin binding may be an

Public Health Relevance

The likely FDA approval of MDV3100 will arm oncologists with two new agents (abiraterone and MDV3100) that can suppress AR activity in CRPC, but patients invariably relapse and resistance mechanisms are unknown. Tis proposal will determine in detail the mechanisms of action for MDV3100 and functionally related AR antagonists under development, and identify mechanisms of .intrinsic and acquired resistance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA163227-01A1
Application #
8475911
Study Section
Project Start
2013-05-24
Project End
2018-04-30
Budget Start
2013-05-24
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$292,751
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Beshiri, Michael L; Tice, Caitlin M; Tran, Crystal et al. (2018) A PDX/Organoid Biobank of Advanced Prostate Cancers Captures Genomic and Phenotypic Heterogeneity for Disease Modeling and Therapeutic Screening. Clin Cancer Res 24:4332-4345
Russo, Joshua W; Liu, Xiaming; Ye, Huihui et al. (2018) Phosphorylation of androgen receptor serine 81 is associated with its reactivation in castration-resistant prostate cancer. Cancer Lett 438:97-104
Mostaghel, Elahe A (2018) Alternative Acts: Oncogenic Splicing of Steroidogenic Enzymes in Prostate Cancer. Clin Cancer Res :
Uo, Takuma; Plymate, Stephen R; Sprenger, Cynthia C (2018) The potential of AR-V7 as a therapeutic target. Expert Opin Ther Targets 22:201-216
Arai, Seiji; Jonas, Oliver; Whitman, Matthew A et al. (2018) Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis. Clin Cancer Res 24:5458-5470
Viswanathan, Srinivas R; Ha, Gavin; Hoff, Andreas M et al. (2018) Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing. Cell 174:433-447.e19
Russo, Joshua W; Gao, Ce; Bhasin, Swati S et al. (2018) Downregulation of Dipeptidyl Peptidase 4 Accelerates Progression to Castration-Resistant Prostate Cancer. Cancer Res 78:6354-6362
Sowalsky, Adam G; Ye, Huihui; Bhasin, Manoj et al. (2018) Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations. Cancer Res 78:4716-4730
Zhu, Yezi; Sharp, Adam; Anderson, Courtney M et al. (2018) Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer. Eur Urol 73:727-735
Penning, Trevor M (2018) Dehydroepiandrosterone (DHEA)-SO4 Depot and Castration-Resistant Prostate Cancer. Vitam Horm 108:309-331

Showing the most recent 10 out of 90 publications