Once again, the prostate cancer community has been rocked by startling and conflicting news. According to a research study from The Johns Hopkins School of Medicine androgen deprivation therapy (hormone blockade- ADT) may encourage prostate cancer cells to produce Nestin, a protein that makes prostate cancer cells more likely to spread through out the body!
Androgen therapy (ADT) is the main stay therapy for men with advanced prostate cancer as well as for men who need to shrink the size of their prostate prior to primary radiation therapy. Now we are being told that hormone therapy might be encouraging the spread of our disease.
David Berman, an assistant professor of Pathology, Urology and Oncology at Johns Hopkins, found that androgen deprivation therapy (ADT) allows for an increase in the gene that causes the expression of Nestin. When they removed the androgens from the chemical soup the human prostate cancer cells were living in, their production of Nestin increased and the prostate cancer cells were able to more easily move around and through other cells.
They further found by reducing the presence of Nestin, prostate cancer cells were not able to move around and through other cells as efficiently. Prostate cancer cells with hampered Nestin expression were less likely then normal cells to migrate to other parts of the body when transplanted unto mice.
Tumor cells from men who never received ADT did not show any sign of Nestin, including those men who had developed metastasizes.
Berman stated that Nestin is produced by prostate cells in response to ADT when the therapy has been used for periods longer than six months. The Nestin may encourage the cells to metastasize.
Berman and his team did go on to say that, their research is far too preliminary for men to stop using ADT. However, this research might change how some physicians elect to treat.
This research was published in the October 1, 2007 issue of Cancer Research.
Joel T Nowak MA, MSW
A well done summary of our work. Thank you Joel. I’d like to elaborate with the hope that I can make this news a little less startling and conflicting.
Let’s start with “Berman stated that Nestin is produced by prostate cells in response to ADT when the therapy has been used for periods longer than six months.”
We examined tissue from a cohort of men who had received androgen deprivation therapy (ADT) for a brief period prior to prostatectomy (usually 6-12 months). In this cohort, we NEVER detected Nestin. In contrast, we detected Nestin in 75% of a second group of men — all of whom died with widespread metastatic prostate cancer and all of whom had received ADT. So ADT is extremely low risk for inducing Nestin in one population, and high risk in the other.
What does this mean for patient care? Well accepted uses of ADT should remain in place until we develop more effective systemic therapies. ADT prior to radiation has been shown to make radiation more effective — it decreases the risk that cancer will recur after radiation. I think it is very important for men planning this therapy to first receive ADT.
In the setting of symptomatic prostate cancer metastasis, ADT provides substantial relief for most patients. This relief may be long-lasting, but is never truly permanent, since a proportion of prostate cancer cells can survive without androgen. It has been known for a very long time but not well-understood that this androgen-independent subset of cancer cells eventually begins to grow again in most patients. At this point, the cancer has changed and ADT is no longer effective. Nestin appears to be part of this change in most patients and also appears to promote cancer spread. Again, using ADT in this setting important.
As for other uses of ADT (intermittent use, use in asymptomatic PSA recurrence, etc.), we have not studied these patients and will need to determine when and if these regimens induce Nestin production.
The good news is that we now have new tool to investigate the events that turn on Nestin production in metastatic cancer and to identify ways to neutralize its role in cell movement. Nestin thus provides a new foothold in the effort to find more effective strategies to treat metastatic prostate cancer.