Slamming the brake on prostate cancer growth

Grant information

Researcher - Dr Nicholas Leslie
Institution - Heriot Watt University
Grant award - £300,626
Status - Complete
Reference - PG14-006

Why did we fund this project?

• Cancers such as prostate cancer form when cells start to divide uncontrollably. To prevent this, cells produce tumour suppressors, that act as an ‘emergency brake’ to stop the cells dividing too much.
• When cells develop into cancer, they often stop producing these tumour suppressors, releasing the brake, and allowing the cancer cells to divide very rapidly.
• One important tumour suppressor is called PTEN. Prostate cancer cells often stop producing PTEN, and this helps prostate cancer to grow and spread.
• Dr Nicholas Leslie and team wanted to understand exactly how PTEN puts the brake on cell division, and how this brake fails in prostate cancer.
• The team think PTEN is only one component of the ‘emergency brake’. In this project, the team wanted to identify the other components that work together with PTEN.
• This could identify targets for new drugs that could put the brake back on, to slow the growth and spread of prostate cancer.

What did the team do?

• The team made mouse models where the prostate cells produced different edited versions of PTEN.
• These edited versions of PTEN could only interact with a limited number of other ‘brake components’ compared to normal PTEN.
• They compared how often mice with edited PTEN and mice with normal PTEN developed prostate cancer, and how aggressive these cancers were.
• This helped them pinpoint the most important components of the ‘emergency brake’, that would be the best targets for treatments.

What did the team achieve?

• The team uncovered that the interaction between PTEN and another brake component called AKT is crucial to stopping the growth and spread of prostate cancer.
• Mice with an edited version of PTEN that could not interact with AKT developed lots of prostate cancers. Contrastingly, mice with an edited version of PTEN that could interact with AKT, but not other components, did not develop cancer.
• This shows that AKT could be a promising target for prostate cancer treatments.

What does this mean for men?

• This project suggests that drugs targeting AKT could be effective treatments for prostate cancer.
• This work supports the evidence behind recent clinical trials of drugs targeting the PTEN 'emergency brake'. One such drug has now been approved to treat breast cancers with certain genetic changes, and researchers are now carrying out trials to test whether these treatments might benefit men with prostate cancer too.