Understanding enzalutamide resistance to help find new treatments

Grant information

Reference: RIA24-ST2-005
Lead researcher: Professor Imran Ahmad
Institution: University of Glasgow
Award: £512,319

What you need to know

• Some men with advanced prostate cancer stop responding to the hormone therapy enzalutamide. This project explores why that happens.
• The researchers are focusing on two genes that normally help keep cancer growth in check. When these genes are faulty or missing, the cancer can become resistant to treatment.
• By studying these changes, the team hope to find new targets for future treatments, as well as tests to help men get more personalised treatment options.

Why are we funding this research?

Advanced prostate cancer is often treated with hormone therapies like enzalutamide, which work by blocking signals that help the cancer grow. But for some men, the cancer finds a way around this and starts growing again - this is called treatment resistance, and it leaves these men with few options to manage their cancer.

Right now, we don’t fully understand why this happens or how to stop it.

By understanding how cancer cells' genes affect treatment resistance, the team hopes to find new ways to spot it early, possibly through a simple blood or urine test, and to develop better treatments that work even when enzalutamide doesn’t.

What will the researchers do?

The researchers are trying to understand why some prostate cancers stop responding to a key treatment called enzalutamide. To do this, they’re focusing on two genes, called RNF43 and ZNRF3, that normally help keep cancer growth under control. When these genes are faulty or missing, the cancer seems to become more aggressive and harder to treat.

To explore this, the team will study samples from men with advanced prostate cancer to see how often these genes are damaged and what effect that has on the cancer. They’ll also grow cells and mini tumours in the lab that mimic what happens in the body when these genes go wrong. These models will help them watch how the cancer behaves over time, especially when it’s exposed to enzalutamide.

To do this, they’ll use cutting-edge tools to track changes in the cancer’s signals and behaviour, looking at how it grows, spreads, and responds to treatment.

Eventually, by comparing cancers with and without these gene changes, they hope to spot patterns that could lead to new ways of diagnosing and treating the disease. For example, do cancers with these changes rely more heavily on particular cellular mechanisms that a future treatment could target?

They also hope to use this information to develop tests, like blood or urine tests, that could help doctors spot resistance earlier and tailor treatments more effectively.

How will this benefit men?

Right now, when a drug like enzalutamide stops working, there aren’t many options left.

If the researchers can understand how these genes affect the cancer’s behaviour, they could help doctors spot resistance earlier – possibly through a simple blood or urine test. That means men could switch treatments sooner, before the cancer gets worse.

It also opens the door to new treatment combinations that might keep the cancer under control for longer. So instead of a one-size-fits-all approach, men could get treatments tailored to how their cancer is behaving.