Download PG12-03 Crabb Lay summary Principal Investigator: Dr Simon

PG12-03 Crabb Lay summary
Principal Investigator: Dr Simon Crabb, Senior Lecturer in Medical
Oncology at the Cancer Sciences Unit, University of Southampton
Lay title:
Can we develop a new hormonally targeted treatment for prostate cancer?
What are you proposing?
We have applied for funding to continue preliminary work, which we describe below, which might provide an
entirely new therapeutic approach for treating prostate cancer. We wish to test this strategy more fully in our
laboratory to allow us to clearly understand the biological activity of these potential new drugs.
Why are you proposing it?
Prostate cancer is an important health concern in the UK where it still causes about 10,000 deaths annually.
Previous advances mean many men never require treatment or are cured. However 20-30% present with
metastatic disease (spread to distant sites beyond the prostate) or develop it subsequently. When the disease
becomes incurable in this way patients are treated initially with hormonal therapies.
Hormonal therapies deplete or block the effects of hormones such as testosterone which stimulate 'androgen
receptors' on prostate cancer cells. Androgen receptors are critical in causing prostate cancer cells to grow.
This is usually very effective but unfortunately most prostate cancers will become resistant to this approach
over time. We therefore have a pressing need for improved treatments.
Our research group have undertaken preliminary work looking at the effects of targeting an enzyme called
LSD1 in prostate cancer. LSD1 is known to contribute to 'activation' of androgen receptors. Chemist
colleagues with whom we collaborate have created a number of new chemical compounds (based on an old
fashioned anti-depressant called tranylcypromine) that inhibit the activity of LSD1. We found that these
compounds inhibited the growth of prostate cancer cells in the laboratory. They appeared to do this, at least in
part, by inhibiting the activity of androgen receptors and also seemed to interact favourably with current and
emerging hormonal treatments for the disease.
How are you proposing to do it?
We are proposing a laboratory based project to understand in detail the mechanisms by which new drugs that
target LSD1 would work in prostate cancer. This will be critical to further development.
How long will it take?
We are asking for 24 months of funding to undertake the proposed work in this application.
What is the budget?
£112,802
What are the expected outcomes?
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).
This work will allow us to select the best candidate compounds to develop further, to understand how they
actually act on prostate cancer cells and how it might be tested in clinical trials in the future.
How could it make a difference to the lives of men affected by prostate
cancer?
We have seen major recent advances in hormonal therapies for this disease but they all become ineffective
over time. Our proposal would build on knowledge of how to target the androgen receptor. We hope ultimately
this would provide an entirely new treatment approach for prostate cancer.
Please write a summary of the project in one sentence only.
We have exciting pilot data of a potential new treatment strategy for prostate cancer and we now wish to
undertake work to understand these experimental drugs better to facilitate their future development.