In this grant, Dr Armstrong aims to develop new drugs to use alongside radiotherapy for prostate cancer and reduce the risk of recurrence after treatment.
Around 30 per cent of men with localised prostate cancer have a mutation in a gene called PTEN, whose normal job is to stop cells like cancer cells growing out of control. Unfortunately for men with this mutation, their cancer is more likely to come back after radiotherapy treatment, and when it does, it’s likely to spread outside the prostate.
Dr Armstrong’s previous work has suggested that prostate cancers missing PTEN function have a high number of immune cells within the tumour. When these cancers are exposed to radiation, the immune cells release proteins that help the cancer cells to escape outside the prostate, and avoid radiation-induced cell death. Drugs against these proteins, including one Dr Armstrong discovered during his PhD, are now being tested in clinical trials, and will hopefully improve response to radiotherapy in men without a PTEN gene.
Dr Armstrong also identified another protein that’s released by immune cells within a PTEN – mutant prostate cancer. This is called YKL40, and he’s already shown that it can promote prostate cancer cell movement and spread. In this project, Dr Armstrong will further investigate how YKL40 helps the cancer cells escape, to see whether this might also be a useful protein to target with new drugs to improve radiotherapy for men with PTEN-mutated prostate cancers.
As part of this Fellowship, Dr Armstrong will travel to The University of Washington in the USA, where he will spend time in Professor Colm Morrissey’s lab there. Professor Morrissey is an expert in the biology and use of 3D model systems to study prostate cancer spread to the bone. Dr Armstrong will use his time there to understand how to make models of prostate cancer bone metastases. Dr Armstrong has also established, a clinical collaboration in Belfast that will enable him access bone fragments from patients undergoing hip replacement surgery. He will then use these models to investigate whether YKL40 also encourages prostate cancer cells to invade and survive within the bone.
Overall, this work could result in not only a new combination treatment for men at risk of cancer recurrence after radiotherapy, but also an in depth understanding of the biology and mechanisms involved in prostate cancer spread to the bone in the 30 per cent of men with prostate cancer who have a mutation in the PTEN gene.
Researcher – Dr Chris Armstrong
Institution – Queen's University Belfast
Grant award – £293,368.00
Reference – TLD-PF16-002