A new hormone therapy for advanced prostate cancer

Grant information

Reference: RIA21-ST2-003 
Researcher: Professor Tim Skerry and Dr Gareth Richards 
Institution: University of Sheffield 
Duration: 2022-2025
Award: £446,629

Why did we fund this project?

• Men with prostate cancer have higher levels of a hormone called adrenomedullin (or AM) in their blood.
• Researchers have shown AM can drive the growth of prostate cancer, and help cancer come back after treatment. This suggests a drug that can block AM could be an effective prostate cancer treatment.
• However, AM also has lots of other roles in the body, including regulating blood pressure. Completely blocking it would therefore cause serious side effects.
• Importantly, there are two different ‘sensors’ for AM found in the body. Sensor 1 is found throughout the body and is essential in regulating blood pressure, whilst sensor 2 is mainly found in cancer cells, and drives the growth of cancer.
• In this project, Professor Tim Skerry, Dr Gareth Richards and team wanted to test whether a new drug that can block only sensor 2 could be an effective treatment for prostate cancer, whilst avoiding any serious side effects. They also aimed to understand which men might benefit most from this treatment.

What did the team do?

• The team compared the levels of AM in the blood of men with and without prostate cancer, and before and after a treatment called hormone therapy had stopped working.
• The team also tested a new drug that can block sensor 2 on mouse models of prostate cancer, and prostate cancer cells grown in the lab.

What did the team achieve?

• The team found that the level of AM was higher in the blood of men for whom hormone therapy had stopped working. This suggests AM could be linked to the effectiveness of hormone therapy.
• Excitingly, blocking sensor 2 with the new drug was able to kill cancer cells and shrink tumours in many of the prostate cancer models tested.
• Importantly, the drug worked much better against some prostate cancer cells compared to others. This suggests more understanding is needed to be able to predict which men will benefit most from this treatment.

What does this mean for men?

• The team have found a link between AM levels and how men respond to hormone therapy. This suggests testing men's AM levels could help doctors identify if men are developing resistance and should be offered another treatment.
• This project has built evidence that targeting AM sensor 2 with a new drug could offer a much-needed new treatment option for men with advanced prostate cancer.
• The team now need to continue to improve their new drug, and understand more about how it works and which men will benefit most. They hope to have developed a drug to test in a clinical trial within the next 5-8 years.