Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment
Abstract
The purpose of this proposal is to examine how senescence in the prostate may be caused by medical treatments for prostate cancer, and to identify senescence-associated factors which may mediate resistance of neoplastic epithelium. The effects of standard and targeted therapeutics on senescence-mediated resistance will be determined. To date, our major findings present a mixed picture of chemotherapy-induced senescence. Senescence-associated-galactosidase staining has not identified significant chemotherapy-induced senescence, but quantitation of gene expression changes reveal a pervasive pattern of senescence changes. Assays for additional markers of senescence and senescence-associated factors have been optimized and validated on a Tissue Microarray of Aging and Prostate Cancer. Correlation of chronological aging and senescence is seen. These assays will be used next on chemotherapy-treated tissues. Finally, our clinical trial of neoadjuvant anti-IGF-1R antibody therapy with combined androgen deprivation prior to prostectomy will examine the clinical effects of abrogating a pathway which is altered in senescence.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA484748
Entities
People
- James Dean
Organizations
- Fred Hutchinson Cancer Center