Studying how androgen receptor variants cause resistance

Grant information 

Researcher - Dr Luke Gaughan
Institution - Newcastle University
Grant award - £99,862.32
Duration - 2015-2018
Status - Completed
Reference – S14-007

Why did we fund this project?

• Prostate cancer cells use hormones to grow rapidly. Blocking these hormones using hormone therapy is used as a treatment to slow down prostate cancer growth in men.
• However, eventually men become resistant to hormone therapy, as cancer adapts to be able to grow without hormones.
• Researchers think this resistance is caused by proteins called androgen receptor variants, or AR-Vs. These proteins tell cells to grow rapidly, even without any hormones being there.
• Dr Luke Gaughan and team wanted to understand how AR-Vs can cause resistance, and find out what other proteins they work together with to help cancer grow.

Project in a nutshell

• The team created prostate cancer cells that they could grow in the lab, that contained lots of AR-Vs.
• They then studied these cells to find out how these AR-Vs are causing resistance.
• They also looked at which other proteins the AR-Vs are interacting with, and so could be working with them to make prostate cancer grow and evade hormone therapy.

What did the team achieve?

• The team successfully created a new model of prostate cancer cells with lots of AR-Vs. 
• Using their new cells, they found a protein called SUMO interacts with AR-Vs and helps them cause resistance. 
• By blocking a protein called PARP, they could make the cancer cells produce fewer AR-Vs, and this makes them grow less quickly. 
• They saw that AR-Vs can make cells resistant to radiotherapy, by stopping cells dying when their DNA is damaged.

How will this benefit men?

• The team have gained insight into how AR-Vs cause resistance, and identified new treatment targets.
• They hope this will lead to the development of new drugs that could stop, or even reverse, resistance to treatments.
• They have also developed new tools that will be useful to help other groups study treatment resistance, which could lead to further discoveries and new treatments.