Standard therapy for prostate cancer, the third-leading cause of cancer-related deaths in American men, is based on blocking androgens, the male sex hormones. However, for some men, prostate cancer recurs despite androgen-deprivation therapy. A team of scientists led by Irwin Gelman, PhD, Professor of Oncology in the Department of Cancer Genetics at Roswell Park Cancer Institute, has identified an 11-gene signature unique to advanced recurrent prostate cancer that they believe will help to identify these aggressive and potentially fatal prostate cancers sooner. The findings have been published online ahead of print in the journal Oncotarget.
For this analysis, Roswell Park researchers measured genes that were specifically induced in human prostate cancer cells by the Src oncogene, a known driver of metastatic progression and recurrence in this disease. They compared these genes to genes that are only active in prostate cancer cells and tumors that have recurred after androgen-deprivation therapy. Through this process, the scientists identified an 11-gene signature that is unique to advanced recurrent prostate cancer.
The researchers also characterized how the Src oncogene drives recurrent prostate cancer through direct activation of the androgen receptor, thereby allowing it to function even after therapy has removed detectable levels of serum androgens. They found that this 11-gene pattern is a biomarker that correlates with a more rapid progress to metastasis and decreased overall survival from prostate cancer.
“This study adds to our understanding of why some men experience metastatic progressive disease after androgen-deprivation therapy,” says Dr. Gelman. “Our data strengthen the idea that combining therapies that inhibit the oncogene Src with those that constrain the androgen receptor may help prevent recurrence of aggressive, lethal prostate cancer.”
Reference: Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures. Oncotarget accessed on line impactjournals.com.