Dear Wonderfully knowledgeable friends,
I've been reading without posting for a while, and you guys have helped me enormously...thank you so much.
Just read the following that might be of interest to those undergoing treatment...if I can find the link (memory does not seem to be serving today), I will post it.
There is something "that can make an already recurrent cancer even more deadly, scientists say. BRN4 is mostly expressed in the central nervous system and inner ear, but now scientists have the first evidence it's amplified and overexpressed in patients with the rare but increasing neuroendocrine prostate cancer, they report in the journal Clinical Cancer Research. As their name implies, neuroendocrine cells also are more common in the brain, but the walnut-sized prostate gland also has a small percentage of them and they appear to become more numerous and deadly in the face of newer, more powerful hormone therapy.
The sex hormone androgen is a major driver of prostate cancer so hormone therapy to suppress it or its receptor -- called chemical castration -- is a standard frontline therapy, says Dr. Sharanjot Saini, cancer biologist in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.
Still as high as 40 percent of patients develop castration-resistant prostate cancer within a few years. This more aggressive cancer is harder to treat, and patients may get a newer, more powerful hormone therapy like enzalutamide, which was first approved in 2012 for this recurring prostate cancer.
It's the far more common luminal cell type in the prostate gland that typically becomes cancerous, says Saini, the study's corresponding author.
But in the face of this additional, more aggressive treatment, a subset of these luminal cells will differentiate into neuroendocrine prostate cancer, a still-more aggressive disease, says Divya Bhagirath, MCG cancer biologist and the study's first author.
Scientists had no clear idea of how the deadly conversion happens, how to know it's happening or what to do when it does happen until now.
By comparing tissues from both patients with and without this more rare prostate cancer, the scientists found that it was BRN4 overexpression and interaction with another transcription factor in the same family, BRN2, driving the prostate cancer cells to become neuroendocrine prostate cancer cells. BRN2 had already been implicated in this cancer, but the MCG investigators found BRN4 was at much higher levels and appeared to be the instigator, Bhagirath notes.
"We are showing that BRN4 does have a role in driving neuroendocrine differentiation in prostate cancer and it does have a role in prostate cancer," Bhagirath says.
They found that enzalutamide, which blocks androgen receptors, also augments release of these two transcription factors -- more of the BRN4 -- in traveling exosomes, which are essentially nano-sized suitcases in which cells swap components and communication. In this case, the exosomes deliver to luminal cells what they need to become neuroendocrine prostate cancer cells.
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