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Research Highlight | October 16, 2019

New finding sheds light on neuroendocrine prostate cancer progression

Hormonal therapy is an aggressive type of cancer therapy often used to treat men diagnosed with metastatic prostate cancer. But while this treatment improves the overall survival of many prostate cancer patients, in about 20 per cent of cases it leads to the development of an even more aggressive form of the disease known as treatment-induced neuroendocrine prostate cancer (t-NEPC).

The need to understand how t-NEPC progresses is huge: survival after diagnosis is less than one year and as hormone therapies for metastatic prostate cancer become more potent, cases of t-NEPC are more prevalent. That is why a new discovery by a team of TFRI-funded scientists based primarily out of the Vancouver Prostate Centre (VPC), is so important.

In a paper published in European Urology (March 2019), the team led by Dr. Xuesen Dong, a senior research scientist at VPC, defines a molecular mechanism by which prostate adenocarcinoma is transformed into neuroendocrine prostate tumours. According to Dr. Dong, this occurs through a process known as alternative RNA splicing.

“This study links RNA splicing changes with cancer cell immune responses that contribute to therapy-resistant tumour progression by demonstrating that the alternative RNA splicing of a histone demethylase gene BHC80 can promote neuroendocrine prostate cancer progression,” said Dr. Dong.

By discovering that RNA splicing of BHC80 contributes to the development of t-NEPC, the team has identified a potential new avenue for future tests and therapies. For instance, detection of RNA splicing events from patient biopsies could be used as biomarkers for tumour aggressiveness. Likewise, BHC80 could also emerge as a potential target for new treatments, providing a therapeutic opportunity to treat patients with t-NEPC.

“We are excited by the notion that blocking these RNA splicing events by small molecules may possibly be developed into future anti-cancer therapies,” said Dr. Dong.


RNA Splicing of the BHC80 Gene Contributes to Neuroendocrine Prostate Cancer Progression


Yinan Li, Ning Xie, Ruiqi Chen, Ahn R. Lee, Jessica Lovnicki, Emma A. Morrison, Ladan Fazli, Qingfu Zhang, Catherine A. Musselman, Yuzhuo Wanga, Jiaoti Huang, Martin E. Gleave, Colin Collins, Xuesen Dong


This study was partially funded by a Terry Fox New Frontiers Program Project Grant in Targeting the adaptive molecular landscape in castrate-resistant prostate cancer