Reversing the switch from treatable to non-treatable prostate cancer

2018 John Paynter Research Innovation Award

What you need to know

  • Prostate cancer that has spread to other parts of the body initially responds well to hormone therapies. But over time the cancer changes and these treatments stop working.
  • Dr Jason Carroll believes the switch from treatable to non-treatable prostate cancer is triggered by a protein called Ascl1. In this study, he will test if this switch can be reversed using drugs that stop Ascl1 from working.
  • This research could lead to the development of new drugs that keep current treatments working for longer, and stop non-treatable forms of prostate cancer from developing.
We want to understand what triggers the switch from a prostate cancer that responds to hormone therapies, to a cancer that is resistant. In doing so, we hope to find ways to stop this switch happening, and keep men responding to hormone therapies for longer.
Dr Jason Carroll

The challenge of treatment resistance

Hormone therapies work by blocking how prostate cancer grows and spreads. But over time the cancer changes to outsmart these treatments, so they eventually stop working.

Dr Jason Carroll wants to understand what triggers the switch from prostate cancer that responds to hormone therapies, to cancer that is resistant. He will specifically focus on what causes the switch to Neuroendocrine Prostate Cancer, a highly aggressive, non-treatable form of the disease. In doing so, he hopes to find ways to stop this switch happening, and keep men responding to hormone therapies for longer.

Finding the trigger and reversing the switch

Dr Carroll has already identified a protein called Ascl1, which he believes plays a crucial role in how NEPC develops and becomes resistant to hormone therapies.

In this study, Dr Carroll wants to confirm that Ascl1 switches on genes that transform treatable prostate cancer into non-treatable NEPC. He will then test a combination of drugs that stop Ascl1 from working, to see if this reverses NEPC back to a less aggressive, treatable form of the disease.

A new target for better treatments

This research will pave the way for future studies and clinical trials looking at Ascl1 and its role in treatment resistance. It could lead to the development of new drugs that block Ascl1, to prevent deadly forms of prostate cancer like NEPC from developing. This could transform the lives of men on hormone therapy, ensuring their treatments keep working and their cancer stays controlled for longer.   

Grant information

Reference - RIA18-ST2-004
Researcher - 
Dr Jason Carroll 
Institution - University of Cambridge
Award
 £267,414.00

This grant is supported in the memory of John Paynter