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Publications of the Week

Patient-Derived Hormone-Naive Prostate Cancer Xenograft Models Reveal Growth Factor Receptor Bound Protein 10 as an Androgen Receptor-Repressed Gene Driving the Development of Castration-Resistant Prostate Cancer

By March 23, 2018No Comments

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 This week we profile a recent publication in European Urology from the laboratory of Dr.
Yuzhuo Wang
(front, 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 (ADT), as the growth of prostate cancer is largely dependent on androgens (male sex hormones). Eventually, the disease becomes treatment-resistant. Interestingly, the majority of treatment-resistant prostate cancers, also know as castration-resistant prostate cancer (CRPC) still express androgen receptor (AR) even if increasingly powerful “next generation” anti-androgen therapeutics are used. As it’s still unclear how the treatment resistance develops, one of our research foci is to study comprehensive mechanism of how resistance to therapy emerges in prostate cancer enabling us to find therapeutics to delay or block the onset of treatment resistance.

What is the significance of the findings in this publication?

This research directed by Dr. Yuzhuo Wang has led to the development of a panel of unique, clinically relevant experimental models, consisting of patient-derived non-treated prostate cancer grafts in immune-deficient mice, that can be used to study the development of CRPC following ADT of the mice. Using these CRPC progression from hormonal-naïve prostate cancer models, the group have recently discovered that a protein which mediate the cross-talk between proteins, called GRB10, plays a crucial “driving” role in the development of CRPC. Their study for the first time reports GRB10 is a mediator between ADT and the activation AKT pathway, which was known to promote the development of treatment resistance. Now we discover the middle player, i.e. Grb 10 between AR suppression and AKT pathway activation. Moreover, GRB10 with its powerful function in promoting treatment resistance also provides a promising therapeutic target for not only treatment of CRPC, but also preventing the disease from happening.

What are the next steps for this research?

We are currently working on elucidating the comprehensive role of GRB10 in promoting the development of CRPC. We are also studying the functional motif of GRB10 which will guide the development of potential small molecular inhibitors to target GRB10 for the prevention and treatment of CRPC.

This research was funded by:

This study was supported by Canadian Institutes of Health Research, Terry Fox Research Institute, BC Cancer Foundation, Urology Foundation, Prostate Cancer Canada, Mitacs Accelerate, Prostate Cancer Canada-Movember, and China Scholarship Council.


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