Accession Number:

ADA585098

Title:

Targeting the Prostate Cancer Microenvironment to Improve Therapeutic Outcomes

Descriptive Note:

Annual rept. 15 May 2012 14 May 2013

Corporate Author:

FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA

Personal Author(s):

• Sun, Yu

Report Date:

2013-06-01

Pagination or Media Count:

30.0

Abstract:

Therapies designed to damage DNA e.g. chemotherapy and irradiation cure many primary prostate carcinomas PCa and produce significant responses in a subset of advanced metastatic cancers. However, a subset of localized cancers resist genotoxic treatments, and most advanced cancers treated with such therapies eventually progress to a lethal phenotype. Thus, therapy resistance is a major contributor to PCa morbidity and mortality. We want to explore the hypothesis that DNA damaging therapeutics generates responses in benign cell types comprising TME that promote tumor cell survival and enhance resistance. We have assessed the outcome of targeting individual mediators of this microenvironment-derived DDSP---specifically a member of the Wnt superfamily, WNT16B and demonstrated the highly effective neutralization of prostate cancer cell malignancy in vitro by purified anti-WNT16B. We anticipate that suppressing WNT16B will diminish treatment-initiated resistance, and improve in vivo tumor responses. We have established primary mouse prostate fibroblast cell lines and examined their responses including DDSP development upon DNA damage, and demonstrated the potential complication of regulatory mechanisms of DDSP program.

Descriptors:

• *PROSTATE CANCER
• DEOXYRIBONUCLEIC ACIDS
• SECRETION
• THERAPY

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE