This week we profile a recent publication in Cancer Research from the laboratory of Dr.
Yuzhuo Wang (second from right) at the BC Cancer Agency.
Can you provide a brief overview of your lab’s current research focus?
Prostate cancer is the major cause of cancer deaths in North American men. The disease in its early stages (when it is confined to the prostate gland) can be treated with excellent chances for survival. However, when the cancer has metastasized (spread) beyond the prostate it is at present not curable, but may be controlled for many years with androgen deprivation therapy, as the growth of prostate cancer is largely dependent on androgens (male sex hormones). Eventually, the disease becomes treatment-resistant, even if increasingly powerful “next generation” anti-androgen therapeutics are used. In fact, treatment with the latter can lead to transdifferentiation (change) of prostate cancer into “neuroendocrine prostate cancer” (NEPC), a lethal, very aggressive subtype of prostate cancer for which there is currently no effective treatment. Thus one of our research foci in the lab is to study comprehensive mechanistic understanding of how resistance to therapy emerges in prostate cancer enabling us to find therapeutics to delay or block the onset of NEPC.
What is the significance of the findings in this publication?
NEPC research by Dr. Yuzhuo Wang group has led to the development of a unique first-in-field, clinically relevant experimental model, consisting of patient-derived prostate cancer grafts in immune-deficient mice, that can be used to study the development of NEPC following androgen deprivation therapy of the mice. Using this model, they have recently discovered that a heterochromatin gene, called HP1α, plays a crucial “driving” role in the transdifferentiation of prostate cancer into NEPC. Their study for the first time reports an NEPC-specific heterochromatin gene signature that can be applied for precision diagnosis of the disease. HP1α with its early and powerful function in NEPC development and aggressiveness also provides a promising therapeutic target for not only treatment of NEPC, but also preventing the disease from happening.
What are the next steps for this research?
To develop therapeutics targeting the critical driver i.e. HP1α for the treatment and management of NEPC
This research was funded by:
The study is supported by Terry Fox Research Institute, CIHR, and Prostate Cancer Canada