PG12-24 Robson Lay summary
Principal Investigator: Professor Craig Robson, Professor of Molecular
Urology at the Northern Institute of Cancer Research, Newcastle University
Lay title:
Investigating mechanisms of hormone resistance in advanced prostate cancer using new models based on
stem cell culture.
What are you proposing?
We aim to improve the understanding of how advanced prostate cancer becomes resistant to hormone
therapy. We plan to investigate what happens to androgen (a type of steroid hormone) receptor expression, a
key driver of prostate cancer growth, using new stem cell culture models which mimic characteristics of the
environment seen in hormone therapy of advanced prostate cancers.
Why are you proposing it?
The androgen receptor is a key driver of prostate cancer growth that remains active despite hormone therapy
during progression to advanced castration resistant prostate cancer. Embryonic stem cells have special
properties that are shared with cancers such as being able to multiply indefinitely and more rapidly than
normal cells.
Recent research shows that genes essential for these stem cells properties are also found in prostate cancer.
Using special culture methods we can induce the expression of stem cell characteristics within prostate cancer
cells grown in the laboratory, mirroring the pattern seen in patients with advanced cancer. Furthermore, our
preliminary data showed increased androgen receptor is associated with stem cell gene expression. By
investigating how stem cell genes drive cancer growth through the androgen receptor we aim to identify new
ways of preventing its activity.
How are you proposing to do it?
We aim to explore how the stem cell environment affects the androgen receptor and its action using existing
molecular biology approaches, which will shed new light into ways of blocking androgen receptor activity. We
will use human cell lines, maintained long term in the laboratory, and also the culture of fresh human prostate
cells from clinical material to ensure that the findings are as faithful as possible to the biology in patients.
We will also validate any candidate regulator molecules by studying their expression in a large archive of
prostate cancer patient specimens linked to clinical data to inform on any relationship with the aggressiveness
of the disease and its ability to respond to hormone treatments. This will also help us understand which
patients will benefit the most from any potential new treatment developed from our studies.
How long will it take?
36 months
What is the budget?
£209,648
Prostate Cancer UK is a registered charity in England and Wales (1005541) and in Scotland (SC039332). A company limited by guarantee registered number 2653887 (England and Wales).
What are the expected outcomes?
An understanding of new mechanisms of androgen receptor action in advanced prostate cancers will enable
the design of better drugs for treatment of men with currently incurable cancer.
How could it make a difference to the lives of men affected by prostate
cancer?
This study may help to identify treatment targets for those men with prostate cancer that have become
resistant to hormone therapy. In addition, although not the main focus of the work, this study will also build on
our pilot data showing that certain stem cell markers are associated with worse clinical outcomes by
confirming these findings in a larger cohort of clinical samples. This, in time, is seen as a value added initiative
that could inform the design of a clinical trial to help to identify those who are at highest risk of developing the
rapidly lethal form of this disease, before it progresses and has become incurable.
Please write a summary of the project in one sentence only.
An investigation of factors that regulate androgen receptor activity using new stem cell based culture models
mimicking advanced prostate cancer resistant to conventional hormone therapy.