Why do treatments for advanced prostate cancer stop working?

Grant information

Reference: MA-TIA23-009
Researchers and institutions:
Professor Gerhardt Attard, University College London
Dr Ashwin Sachdeva, The University of Manchester
Dr Emily Grist, University College London
Professor Francesca Demichelis, University of Trento
Dr Anna Wilkins, Institute of Cancer Research
Professor Mariam Jamal-Hanjani, University College London
Award: £2,747,929, jointly funded with the John Black Charitable Foundation

What you need to know

Some men with advanced prostate cancer initially respond well to treatment, but later find it stops working, making the disease harder to control.
This project aims to uncover why some treatments stop working and find new ways to keep prostate cancer under control for longer.
The team will do this by studying blood samples, scans and, in some cases, tumour samples after death, from men in a trial called STAMPEDE2.

Why are we funding this research?

Prostate cancer treatments have come a long way, especially for men whose cancer has spread. These treatments can help men live longer, but there’s still a big problem - for many men, the cancer eventually stops responding to them, and we don’t fully understand why this happens. Current trials tell us which treatments work best overall, but they don’t explain what’s going on inside the cancer as it changes over time.

That’s where this project, called STAMPEDE Life, comes in. The research will follow men in a trial called STAMPEDE2, collecting blood samples, scans and, in some cases, tumour samples after death. By studying these in detail, researchers aim to see how prostate cancer evolves and why it becomes resistant to treatments.

This is a new approach because it looks at cancer evolution in real time and across multiple stages, rather than just at diagnosis. The aim is to find patterns that predict how and when the disease will become resistant to treatment, and spot new weaknesses that could be targeted with future treatments, so that men can stay well for longer.

STAMPEDE Life is one of the most ambitious programs conducted internationally to track prostate cancer over the course of different treatments, with the aim of understanding why treatment resistance emerges. With a better understanding of why prostate cancer behaves the way it does, we will be able to develop better treatments tailored for specific patients.

Professor Gerhardt Attard, University College London

What will the researchers do?

The STAMPEDE Life project is running alongside the STAMPEDE2 clinical trial, which is for men whose cancer has spread but is still responding to hormone therapy. As part of the trial, these men are receiving either the current standard treatment for their cancer, or the standard treatment alongside one of two types of radiotherapy. STAMPEDE Life will focus on men getting the kind called lutetium-177 PSMA (also called 177Lu-PSMA), which delivers targeted radiation to prostate cancer cells.

To understand how prostate cancer changes and becomes resistant to these treatments, the STAMPEDE Life team will use a range of innovative approaches. Firstly, they’ll collect blood samples from men at different points throughout their treatment – not just at the start, but after each new treatment and when the cancer begins to grow again. These samples contain fragments of cancer DNA that have broken off from tumours and entered the bloodstream. By analysing this DNA, the researchers aim to spot genetic changes that signal when the disease is becoming resistant to treatment, and track how these changes build up over time.

Alongside blood tests, the team will analyse the men’s scans (such as PSMA PET and MRI) that show where cancer is in the body and how it responds to treatment. Linking these images with genetic data will help reveal whether certain changes in the cancer’s DNA go alongside changes that are seen on scans.

Lastly, for a smaller group of men who consent to donate prostate cancer samples after they die, the research team will use advanced techniques to map the activity of thousands of genes across the different parts of a tumour.

By combining all this information – blood, scans, cell samples and clinical records – the team will build a detailed timeline of how prostate cancer adapts to survive treatment.

How will this benefit men?

In the short term, if the researchers can uncover the changes prostate cancer undergoes to become resistant to treatment, it could lead to new tests that can pinpoint when this happens.

This means doctors could find the men who have stopped benefiting from treatment sooner than is currently possible – potentially enabling them to move onto a new treatment that still works.

In the long run, the research could make it possible to develop new treatments, or new combinations of treatments, that are effective for longer, giving men with advanced cancer more time with their loved ones.