A new prostate cancer treatment enters the fold

Grant information

Why did we fund this project?

• Many effective treatments for prostate cancer work by blocking a protein called the androgen receptor, or AR. The AR helps prostate cancer to grow and spread.
• Unfortunately, over time the AR can adapt its shape to be able to ‘hide’ from these drugs, and they stop being effective.
• Professor Johann de Bono and team proposed a completely new way of stopping the AR in its tracks.
• All proteins, including the AR, are first produced as long, shapeless strands. They need help from other proteins, called ‘chaperones’, to fold them into their true shape, like how someone doing origami folds a flat sheet of paper into complex structures.
• If proteins fold into the wrong shape, they do not work properly, and eventually get destroyed.
• Johann and team are investigating a particular chaperone that is important in helping the AR to fold correctly, and a new drug that could block this chaperone.
• This new drug could make the AR fold into the wrong shape and so get destroyed, stopping it from helping prostate cancer to grow and spread.
• In this project, the team wanted to test this new drug in different prostate cancer models, to see if it could stop the AR in its tracks, and so could be an effective treatment for men.

What did the team do?

• The team studied the effect of their new drug in different prostate cancer models, including cancer cells grown in a dish, and ‘mini-tumours’ grown from prostate cancer tissue taken from men.
• They tested if the drug changed the amount of the AR found in the cells, and if it affected how the cancer cells could survive, grow and spread.

What did the team achieve?

• Excitingly, the team found the drug was able to reduce the amount of the AR in the prostate cancer models, and that this reduced the cancer’s ability to grow and spread.
• The team found blocking the AR was not the only way their drug could slow the growth and spread of cancer. Interestingly, the drug also made the cancer cells enter a ‘stressed’ state, and this further reduced their ability to grow.

What does this mean for men?

• The team have shown this new drug can slow the growth and spread of cancer.
• This drug is currently being tested to see if it is safe for humans. The team hope the findings of this project give them the evidence they need to start a clinical trial in men with prostate cancer.
• The team hope this drug will eventually provide a treatment option for men with advanced prostate cancer that is resistant to other treatments.