PG12-03CrabbLay 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?
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.