Researcher - Dr Nicholas Leslie
Institution - Heriot Watt University
Grant award - £300,626.00
Reference - PG14-006
The researchers are investigating how loss of a gene called PTEN leads to aggressive prostate cancers.
Many prostate cancers – and especially more aggressive tumours – lack a gene called PTEN. PTEN works in part by blocking the function of proteins called AKT and TOR, which help cells to grow and divide. When this process is out of control, it leads to cancer. There are already about 10 new cancer drugs that work by mimicking PTEN and blocking AKT and TOR in clinical prostate cancer trials, but for some reason we don’t yet understand, they haven’t been very successful. In this project, the investigators will investigate whether this is because AKT and TOR aren’t the main drivers of prostate cancer in patients lacking PTEN after all. If that’s the case, they’ll look for the real reason why men lacking PTEN develop prostate cancer. It’s important to know this in order to design drugs to successfully treat aggressive prostate cancers.
The researchers have been working to breed mice with a specific genetic change so that the PTEN protein in the prostate can only perform some of its normal functions. This required at least four generations of mice to be born, so the mice they want to study are still very young. However, the very first results are promising, as the mice have begun to develop prostate cancer, which confirms that the genetic changes in the tumours of prostate cancer patients cause a similar disease in mice. As a key part of the project, the researchers are using a modified version of PTEN that disrupts only certain functions, in order to test which of those functions are linked to cancer formation. They are currently looking at tissue samples from the mice to try and understand the disease process a bit better.