Developing new ways to prevent treatment resistance in prostate cancer

Grant information

Reference: MA-TIA23-001
Researchers: Professor Johann de Bono, Dr Alec Paschalis, Dr Adam Sharp
Institution: The Institute of Cancer Research, London
Award: £1,977,694

What you need to know

• Although today’s treatments for advanced prostate cancer can keep the disease under control for many years, over time these treatments become less effective, allowing the cancer to grow and spread once more.
• This research will target so-called ‘sleeper cells’ – cancer cells that survive treatment and slowly feed tumour growth – which potentially contribute to this treatment resistance.
• The researchers will test a new drug that aims to stop these sleeper cells. If successful, this could make current treatments more effective, leading to longer, better lives for men with advanced prostate cancer.

What will the researchers do?

Current treatments like chemotherapy, radiotherapy and hormone therapy can help manage prostate cancer, but they often leave behind some cancer cells that survive and continue growing.

These ‘sleeper cells’ can pull in white blood cells – which would normally help to fight off cancer – to feed the cancer’s continued growth, block the immune system from killing the tumour, and even help the disease become resistant to treatment.

The research team aims to stop sleeper cells doing this, and so make prostate cancer respond to treatment again, with a clinical trial of a new drug.

The trial is based on previous work where the researchers discovered two critical ‘switches' on the white blood cells that are hijacked by cancer cells. These switches help pull the white blood cells into the tumour, to support cancer growth and make it harder for existing treatments to work.

With this information, the team will utilise a new drug, dubbed SX-682, designed to block both switches from being activated. This drug aims to prevent the white blood cells from being attracted to the tumour, effectively cutting off a key support system for the cancer cells.

This clinical trial will test the new drug on men with advanced prostate cancer.

Firstly, the team will ensure the new drug doesn’t cause significant side effects, maintaining the participants’ quality of life as much as possible.

Next, at the point when a man's current hormone therapy stops working, he will be given the new drug to see if it can stop his white blood cells from entering the tumour and halt the cancer’s growth.

Then, the researchers will use blood tests and biopsies of the cancer cells to monitor how well the drug is working and identify which men benefit the most from this treatment.

By the end of the trial, the researchers hope to show that this approach can clear the cancer of these supportive white blood cells and reverse the resistance that prostate cancer cells have developed, improving the effectiveness of hormone therapies and also chemotherapy.

How will this benefit men?

If successful, this approach could transform how we treat advanced prostate cancer by making existing therapies more durable and effective.

In the long run, the research could lead to more personalised treatment plans, where doctors can identify which men will benefit most from this new strategy. This could not only save and extend the lives of men with advanced prostate cancer, but also significantly improve their quality of life.