Androgen Receptor Action in Castration Resistant Prostate Cancer View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2013-2019

FUNDING AMOUNT

10340608 USD

ABSTRACT

DESCRIPTION (provided by applicant): The past several years have seen a paradigm shift in prostate cancer (PCa) therapy; and it is now becoming widely accepted that androgen receptor (AR) remains active and is a therapeutic target in prostate cancers that relapse after surgical or medical castration (castration resistant prostate cancer, CRPC).'This Program Project brings together a group of investigators with extensive and complimentary expertise in androgens and AR in PCa, and with a track record of accomplishments and productive collaborations. Each project focuses on distinct mechanisms that contribute to AR activity and function in CRPC. Project 1, Steroid Metabolism in Castration-Resistant Prostate Cancer (PI Peter Nelson), focuses on targeting intratumoral androgen synthesis and mechanisms of resistance to abiraterone and other inhibitors of androgen synthesis. Project 2, Basis for Androgen Receptor Antagonist Resistance in CRPC (PI Steven Balk), focuses on mechanisms of action and resistance to AR antagonists. Project 3, Development of Castration Resistance by Alternative AR Splicing (PJ Stephen Plymate) focuses on the role of alternative AR splicing in CRPC. Project 4, Epigenetic Reprogramming of AR Function In CRPC (PI Myles Brown) focuses on the AR transcriptional program and how it is altered with PCa progression. Core A, Administrative/Clinical/Biostatistics Core (PI Steven Balk, Co-PI Peter Nelson) will coordinate the overall program, provide biostatistical support, facilitate access to patient materials, and consult on approaches to enhance/accelerate translation to the clinic. Core B, Biospecimen and Animal Models Core (PI Robert Vessella), will provide a unique series of PCa xenograft models in conjunction with the expertise and infrastructure to carry out trials of single and combination therapies in these models. Dr. Vessella also directs a very robust biospecimen collection and processing Core, and will provide further access to appropriate clinical materials. Core C, Steroid Analytical Core (PI Trevor Penning), will develop and deploy needed state-of-the-art methods to measure multiple steroid and metabolites in human and mouse samples. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=9280881

Related SciGraph Publications

  • 2019-03-19. Association of prostate cancer SLCO gene expression with Gleason grade and alterations following androgen deprivation therapy in PROSTATE CANCER AND PROSTATIC DISEASES
  • 2018-12. Microsatellite instability in prostate cancer by PCR or next-generation sequencing in JOURNAL FOR IMMUNOTHERAPY OF CANCER
  • 2017-07. Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens in NATURE BIOMEDICAL ENGINEERING
  • 2017-03. Systematic and functional characterization of novel androgen receptor variants arising from alternative splicing in the ligand-binding domain in ONCOGENE
  • 2017-03. Role of OATP transporters in steroid uptake by prostate cancer cells in vivo in PROSTATE CANCER AND PROSTATIC DISEASES
  • 2016-12. A proteolytic modification of AIM promotes its renal excretion in SCIENTIFIC REPORTS
  • 2016-11-29. Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer in NATURE COMMUNICATIONS
  • 2016-07. HDAC inhibition impedes epithelial–mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer in ONCOGENE
  • 2016-05. Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy in NATURE
  • 2016-04. Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer in CLINICAL & EXPERIMENTAL METASTASIS
  • 2016-04. Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer in NATURE MEDICINE
  • 2015-09. Role of diet in prostate cancer: the epigenetic link in ONCOGENE
  • 2015-01. Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation in IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY - ANIMAL
  • 2014-12. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer in NATURE COMMUNICATIONS
  • 2014-08. The Link Between Androgen Receptor Splice Variants and Castration-Resistant Prostate Cancer in HORMONES AND CANCER
  • 2014-06. Mechanisms of the androgen receptor splicing in prostate cancer cells in ONCOGENE
  • 2014-05. MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A in ONCOGENE
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