The use of ADT is the treatment of choice for advanced, metastatic prostate cancer as long as the cancer is responsive to the blockade. The theory goes that the suppression of circulating testosterone, which fuels prostate-cancer growth, whether by surgical castration (orchiectomy) or castration with testosterone-blocking drugs slows down the progression of the prostate cancer.
ADT seems to buy additional time for prostate cancer patients, it does not a cure the cancer. Eventually, the cancer becomes resistant to the androgen deprivation therapy (ADT) and continues to grow and spread.
A team of researchers from the Fred Hutchinson Cancer Research Center and The University of Washington School of Medicine, may now be able to explain how prostate tumors eventually become resistant to ADT.
Their discovery is that metastatic prostate tumors are themselves able to generate significant levels of testosterone by themselves! This generation of testosterone is then able to fuel the growth of the cancer.
The surprise was when the researchers found that testosterone levels were four times higher in metastatic tumors from castrate men (collected immediately after death via rapid autopsy) than in benign and cancerous prostate tissue in men with normal circulating androgen levels (collected at the time of prostate surgery).
This finding was reported in the June 1 issue of Cancer Research. I hope that this may lead to the development of better drugs to treat metastatic disease. Currently ADT targets the systemic, or circulating, androgens in men with advanced prostate cancer. Now, we need to search for ways to also target the metastatic prostate-tumor tissue itself as the source androgens.
In addition to measuring androgen levels in distant tumor sites, the researchers also analyzed the gene-expression patterns in the metastatic tissue. The analysis confirmed the presence of the genetic pathways and genetic transcripts that control testosterone production. This presence of this genetic material explains the tumor’s ability to make the proteins that produce testosterone and other androgen hormones.
This research calls for the development of new drug targets. In addition to the systemic suppression we currently utilize, it suggests we also need to target hormone suppression inside the tumor itself. This expanded approach should also improve treatment for patients at all stages of prostate cancer from men with metastatic disease to men with high-risk, localized tumors in which there is concern that small amounts of cancer may have escaped the prostate.
Funding sources for this research included the National Institutes of Health, the Department of Defense and the Prostate Cancer Foundation.
Joel T Nowak MA, MSW
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