Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment
Annual rept. 1 Mar 2008-28 Feb 2009
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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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. 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 and possible links to hepatocyte growth factor in the prostate microenvironment. Finally, our clinical trial of neoadjuvant anti-IGF-1R antibody therapy with combined androgen deprivation prior to prostatectomy will examine the clinical effects of abrogating a pathway which is altered in senescence.
- Medicine and Medical Research