Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment
Abstract
Deaths due to prostate cancer- the second leading cause of cancer death in men in the United States - could be prevented with more effective treatments. Overcoming tumor cell resistance to the effects of androgen deprivation and chemotherapies would significantly improve the morbidity and mortality of prostate cancer. We hypothesize that the induction of cellular senescence in the tumor microenvironment by androgen deprivation and cytotoxic chemotherapy promotes the resistance and survival of carcinoma cells. We further hypothesize that targeting senescence associated pro-survival paracrine factors will enhance the effects of these therapies and enhance response rates. To address these hypotheses, we have three aims: First, to identify senescence changes in prostate tissue induced by androgen deprivation and chemotherapy, specifically focusing on identifying factors with the potential to influence the survival/resistance of neoplastic epithelium via paracrine mechanisms. Second, to evaluate the effects of inhibiting specific senescence associated pro-survival factors using in vivo models. Third, to develop and execute clinical trials designed to inhibit senescence-associated paracrine survival mechanisms and determine if enhanced tumor responses can be achieved.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2011
- Accession Number
- ADA545000
Entities
People
- James Dean
Organizations
- Fred Hutchinson Cancer Center