ACE: testing a new drug for the PTEN-deficient men

What you need to know

  • We need better treatments for advanced prostate cancer, that are precise for each individual man and his cancer.
  • In this study, the team are testing a new treatment for men with a PTEN mutation, that could activate the immune system against their cancer and prevent it from becoming resistant to treatments like enzalutamide.
  • The team are carrying out a combination of research in the lab to learn about the biology of the new treatment, and research in men, to see if the new treatment is safe and effective.
Immunotherapy has had significant benefits in other cancers, but has failed to impact prostate cancer care so far. Our research has the potential to cause a breakthrough in our understanding of the disease and could finally deliver the full potential of immunotherapy against lethal prostate cancer.
Professor David Waugh, Chief Investigator of ACE

What they want to find out

Research has begun to deliver new ways to treat advanced prostate cancer, but we still don’t have enough weapons in our arsenal to beat it. We need to improve our understanding of the genes that drive advanced prostate cancer, and how these genes vary between each man.

A common gene to be altered in men with advanced prostate cancer is called PTEN. Men with a fault in this gene often find that treatments like abiraterone and enzalutamide don’t work very well for them. Previous research suggests that this may be because PTEN-mutated prostate cancers can ‘hide’ from the immune system, stopping it from fighting the cancer. This can also promote resistance to treatments.

In this study Professor David Waugh and Professor Johann de Bono are investigating a potential new treatment for men with PTEN-mutated prostate cancers which could restore the immune system back to full power against prostate cancer.

How they’re going about it

The researchers are combining laboratory and clinical work to test their potential new drug.

First, they want to understand about the basic biology of the drug, and see whether it works in the way they expect it to. They’re testing what happens to the immune system, cancer cell growth, overall tumour size and survival when they use a drug in PTEN-mutated mice. They’re also investigating whether treating the mice with abiraterone at the same time makes any difference to how well this new type of treatment works.

The team are also conducting two trials in men to test the drug. The first is to test how safe this drug is for men. Then they’ll run a second, bigger study to see whether treatment with this new drug can enhance the effect of enzalutamide in men with advanced prostate cancer, so it works better for them for longer.

Throughout these clinical tests, the research team will collect blood and biopsy tissue from the patients, so that they can look back to see whether the men who respond best to the combination of enzalutamide and the new drug are those patients with a mutation in the PTEN gene. This would imply that this combination would be an appropriate first choice for these men.

 

Grant information

Reference - RIA15-ST2-018
Lead Researchers - 
Professor David Waugh and Professor Johann de Bono
Institution - Queen’s University Belfast
Award - £819,364