Targeting androgen receptor modifications to find and treat aggressive prostate cancer

Grant information

Researcher - Professor Joanne Edwards
Institution - Glasgow University
Grant award - £99,758.00
Duration - 2015 - 2018
Status - Completed
Reference – S14-003

Why did we fund this project?

• The androgen receptor, or AR for short, is a protein found in prostate cancer cells. It helps the cells to grow and spread.
• After it has been made by cells, the AR can undergo different modifications. These modifications can make the AR behave in different ways.
• Professor Joanne Edwards and team had previously shown men whose cancer had lots of 2 particular modifications were more likely to have more aggressive cancer and a shorter survival time.
• The team thought these modifications might be increasing the ability of the AR to cause cancer to grow and spread. If so, blocking these modifications could be a new way to treat prostate cancer.
• In this project, the team studied if these modifications could be treatment targets. They also studied if the amount of the modifications predicted how aggressive a prostate cancer would become, and how well it would respond to existing prostate cancer treatments. This would help inform treatment decisions.

What did the team do?

• The team studied the 2 modifications to the AR in prostate cancer cells and animal models of prostate cancer.
• The team studied whether levels of the modifications were linked to more aggressive cancer, and studied how they affected prostate cancer cells’ ability to grow and spread.
• They also tested whether existing prostate cancer treatments could alter the amount of the modifications found in cancer cells.

What did the team achieve?

• The team found the 2 modifications were more common in aggressive prostate cancer. Prostate cancers with high levels of both modifications were particularly aggressive.
• This suggests testing men's cancer for these modifications could help predict which men will develop aggressive cancer.
• Excitingly, the team also found some prostate cancer treatments, such as enzalutamide, reduced the levels of these modifications. This reduces prostate cancer's ability to survive and grow.
• The team think with further validation, these findings could help identify men who are most likely to benefit from drugs like enzalutamide.

How will this benefit men?

• The team have gained important insight in how these 2 modifications of the AR link to aggressive prostate cancer.
• They have also uncovered links between these modifications and treatment effectiveness, that with further validation could help inform treatment decisions for men.