Reversing the switch from treatable to non-treatable prostate cancer

Grant information

Institution – University of Cambridge
Researcher – Professor Jason Carroll
Grant award - £267,414
Duration of funding – 2020-2024
Status - Complete
Reference – RIA18-ST2-004

Why did we fund this project?

• Most prostate cancers grow by using the male hormone testosterone as fuel. Hormone therapies aim to block this supply. Over time, prostate cancers find ways to keep growing without relying on testosterone. When this happens, cancers are said to be hormone therapy resistant. 
• In some men this resistance happens because the cancer changes into a different type of prostate cancer, such as neuroendocrine prostate cancer (NEPC). 
• NEPC is an aggressive form of prostate cancer with limited treatment options, and we still don't fully know how or why it develops. 
• We funded Professor Jason Carroll to study NEPC - to see if we can force NEPC back into a treatable form of prostate cancer.

What did the researcher do?

• Jason and his team wanted to understand the specific proteins made by the prostate cancer that drive NEPC growth, and whether these proteins can be blocked to stop NEPC developing. 
• They focused on a specific prostate cancer protein called ASCL1 - a protein known to play an important role in other types of cancer. 
• The team also looked into other proteins produced by prostate cancer that could be involved in the development of NEPC. 
• In the laboratory, the team tested combinations of drugs that stop these proteins from working, to see if they could slow down or stop the development of NEPC. 

What did the researcher achieve?

• Excitingly, the team found around 70 proteins produced by the prostate cancer that could play a role in NEPC development - meaning 70 potential drug targets. 
• When the team tested drugs to block ASCL1 in the laboratory, they did not detect a strong effect on slowing down the growth of NEPC. However, promising early results suggest blocking one of the 70 new drug target proteins - a protein called p300 - may slow the growth of NEPC. 
• Further research is now being carried out by Jason and his team to understand whether blocking the new p300 target protein stops the development of NEPC. 

How will this benefit men?

• NEPC is difficult to treat, so preventing its development is crucial in helping men with prostate cancer live longer lives. 
• Importantly, Jason's research has advanced our understanding of NEPC and uncovered 70 potential new drug targets, opening up many more avenues to be explored. 
• These findings could support the development of new drugs that stop NEPC growth, potentially helping hormone therapies work for longer in men with prostate cancer.