Researchers in the Faculty of Medicine and the Vancouver Prostate Centre have identified the key protein linked to neuroendocrine prostate cancer (NEPC), a highly aggressive cancer that sometimes emerges in patients undergoing androgen deprivation therapy.
Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Since prostate cancers rely on androgen as a fuel for growth, the drugs target androgen receptors and starve the cancer cells. But for some men, the androgen deprivation treatment has a deadly outcome. In these patients, the treatment causes their prostate cancer cells to become resistant and change into much more lethal ones. As more prostate cancer patients are treated with anti-androgen drugs, the number of cases of NEPC is growing.
Amina Zoubeidi
“We estimate between 12 and 20 per cent of patients treated with androgen deprivation therapy go on to develop NEPC,” said Amina Zoubeidi, an Associate Professor in the Department of Urologic Sciences and a research scientist at the Vancouver Coastal Health Research Institute.
Dr. Zoubeidi and her team of researchers designed a mouse model of NEPC to identify a key protein, called BRN2, that was essential for NEPC to develop. The researchers then went on to study human tissue samples from patients with NEPC, and found that BRN2 was also highly expressed in those samples.
“These are significant numbers,” said Dr. Zoubeidi, whose findings were published in Cancer Discovery and highlighted in Nature Reviews Urology. “Up until now we weren’t able to answer why these cells were becoming so aggressive in some patients. Now we have an answer.”
Dr. Zoubeidi’s team then used state-of-the-art CRISPR technology to turn off the BRN2 gene. When they did so, they prevented the emergence of NEPC. Researchers at the Vancouver Prostate Centre are now developing an inhibitor drug that will turn off BRN2 in prostate cancer patients and block the growth of NECP.