Although there are treatments for early prostate cancer, these will not work for some men with high-risk prostate cancer, and the disease will relapse. Returning prostate cancer often spreads outside of the prostate, and becomes resistant to hormone-therapies, meaning it is incurable. Professor Waugh wants to improve the effectiveness of the first prostate cancer treatments, so that fewer men’s cancer relapses, and more people survive prostate cancer.
Many of the men whose prostate cancer relapses have a mutation in a gene called PTEN, which Professor Waugh is also studying in another project funded by Prostate Cancer UK. He and his team think that mutations in PTEN help prostate cancer tumours to become inflamed, which causes the cancer to spread around the body and become treatment-resistant. A new drug called ASTX660 acts to prevent these effects of inflammation, and previous research shows it weakens the prostate cancer, so that it can be killed more easily by standard treatments. In this project, Professor Waugh wants to learn more about how this happens, and to see if ASTX660 could be used in combination with standard treatments to treat PTEN-mutated cancers.Professor Waugh will start by testing ASTX660 in the laboratory, in prostate cancer cells and mice, to see if it can be combined with standard treatments like radiotherapy and hormone therapy to make them more effective at killing cancer cells.
If this is true, Professor Waugh will test his drug in men for the first time, to see if it is safe when combined with radiotherapy, and is delivered to the right areas of the body. This is an exciting first step that could lead to ASTX660 being tested in larger clinical trials and potentially be used to treat men with prostate cancer.
The team will also use biomarkers, molecules that can be detected in blood, urine or tumour samples, to confirm that the drug works in the way that they have predicted. They will also find biomarkers that could be used to identify men that have PTEN mutations, and so would be suitable to take part in clinical trials and use the drug in the future. Finally, by doing work to understand how ASTX660 works, the team may also find new routes for future drug development.
Reference - PG14-007-TR2
Researcher - Professor David Waugh
Institution - Queen's University Belfast
Award - £482,319.00