Finding a new treatment to delay enzalutamide resistance

What you need to know

• Researchers are studying a new way to treat advanced prostate cancer – one that has already shown promise in other cancers. 
• The treatment is aimed at preventing, reversing, or delaying resistance to existing prostate cancer treatments such as enzalutamide. 
• The goal is to extend the duration and quality of life for men with prostate cancer. 

What will Professor Mongan and his team do?

The researchers will look at why hormone therapies like enzalutamide eventually stop working, and whether it is possible to keep this from happening with a new kind of treatment. 

Enzalutamide works by stopping prostate cancer cells from being able to use the hormone testosterone, which the cells need to grow. It does this by blocking up the part of the cancer cell that would normally respond to testosterone, so that when testosterone does arrive at the cancer cell, it can’t kick-start the processes that would cause the cell to grow. 

However, Professor Mongan has found evidence that prostate cancer cells eventually adapt to hormone therapy by developing differently shaped components that cannot be blocked by enzalutamide. This means that the cells can once again respond to testosterone, and the treatment stops working. 

Professor Mongan and his team believe that prostate cancer cells do this by adapting a process called RNA methylation to their advantage. RNA methylation can change how the instructions for how to make parts of a cell – such as the part that responds to testosterone, are used in the cell.  

The team will test their theory by studying RNA methylation in cells from men with prostate cancer as well as in lab-grown prostate cancer cells – and whether differences in RNA methylation are linked to those cells no longer responding to treatment.  

As there are already drugs being developed that target RNA methylation in other types of cancer, the team will also look at whether these drugs can prevent or reverse resistance to hormone therapy in cancer cells, and potentially extend the benefits of these treatments.

How will this benefit men?

The research should give us a much better understanding of how prostate cancer becomes resistant to hormone therapies like enzalutamide. This could lead to new ways to improve hormone therapy so that it lasts longer and is less likely to encourage resistance. 

The project could also lead to clinical trials of new treatments for advanced prostate cancer that target RNA methylation and so prevent or reverse resistance to hormone therapy.  

In doing so, these treatments could help men with advanced prostate cancer live longer, healthier lives. 

Grant information

Reference: RIA21-ST2-002 
Researcher: Professor Nigel Mongan 
Institution: University of Nottingham 
Award: £259,206