Accession Number:

AD1058801

Title:

Identifying Androgen Receptor-Independent Mechanisms of Prostate Cancer Resistance to Second-Generation Antiandrogen Therapy

Descriptive Note:

Technical Report,01 Aug 2015,31 Jul 2017

Corporate Author:

Memorial Sloan Kettering Institute for Cancer Research New York United States

Personal Author(s):

• Wise, David

Report Date:

2017-10-01

Pagination or Media Count:

13.0

Abstract:

We hypothesize that GR mediates resistance to enzalutamide in advanced prostate cancer through transactivation of SGK1 and activation of a non-luminal gene expression program. In this proposal, we aim to further explore the relationship between GR, SGK1, and enzalutamide resistance through experimental manipulation of GR and SGK1 in our previously reported laboratory models of enzalutamide resistance. In this research period, we engineered a CRISPR-mediated SGK1 deletion model of enzalutamide-resistant prostate cancer and observed modest reduction in tumor growth in response to enzalutamide. Our observation that SGK1 correlates with loss of AR signaling and EMT directly led us to the discovery that the immunomodulatory Wnt regulated cytokine,DKK1, is upregulated in AR-independent prostate cancer. We are currently validating whether DKK1 can be a useful biomarker and therapeutic target of this disease subtype.

Descriptors:

• prostate cancer
• neoplasms
• proteins
• gene expression
• prostate
• therapy
• cell line
• biological markers
• androgens
• tissues
• clinical trials
• cytokines
• culture techniques
• amino acids
• peptides
• and proteins
• RECEPTOR SITES (PHYSIOLOGY)
• drug resistance

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE