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. To date, our major findings present a mixed picture of chemotherapy-induced senescence. Senescence-associated Beta-galactosidase staining has not identified significant chemotherapy-induced senescence, but quantitation of gene expression changes reveal a pervasive pattern of senescence changes. Correlation of chronological aging and senescence is seen. Detailed investigations into a putative secreted marker of senescence, STC1, find significant decreases in cancer compared to benign prostate glands, establish STC1 secretion as a response to numerous microenvironmental stressors including chemotherapy, and find increased STC1 expression in human prostate tissue after neoadjuvant chemotherapy. Finally, abrogation of the senescence-associated IGF pathway is being tested in a clinical trial of neoadjuvant anti-IGF-1R antibody therapy with combined androgen deprivation prior to prostatectomy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2010
- Accession Number
- ADA525781
Entities
People
- James P. Dean
Organizations
- Fred Hutchinson Cancer Center