A failed Alzheimer's drug could boost effect of radiotherapy on brain tumours

27th January 2023

A new clinical trial is set to launch this year that could help more patients with brain tumours benefit from radiotherapy. Dr Manuel Valiente and his team in Spain were recently supported by Worldwide Cancer Research to investigate how brain tumours resist radiotherapy. Now, the incredible breakthroughs they made are kick-starting a clinical trial that could bring new hope for the future of brain tumour treatment.

Breakthrough in brief:

Dr Manuel Valiente and his team in Spain have been studying brain tumours and why some patients don’t respond to radiotherapy.

Your support helped them make a breakthrough. They identified a drug, called a RAGE inhibitor, that could block the process that makes brain tumours resist radiotherapy.

This has led to a new clinical trial, due to start this year. It will test a combination of radiotherapy and the RAGE inhibitor in patients with glioblastoma.

If successful, a new personalised approach could mean that more patients with brain tumours benefit from radiotherapy.

Brain tumours can resist radiotherapy

Brain tumours can be difficult to treat, whether caused by cancers like glioblastoma that start in the brain, or when cancer from elsewhere in the body spreads to the brain (brain metastasis). In fact, brain tumours are the leading cause of cancer death in children and adults under 40.

Radiotherapy is one of the gold-standard treatments for brain tumours, however not all patients respond as hoped – their cancer resists the radiotherapy and continues to grow.

Dr Manuel Valiente, Worldwide Cancer Research scientist, lead author of the study
The very first funding I got for this project was from Worldwide Cancer Research. By investing in projects in early development, you open completely new windows to change things.

From new idea to big breakthrough

In 2018, Dr Manuel Valiente came to us with an idea about this problem. He and his team at the Spanish National Cancer Research Centre (CNIO) had discovered a potential link between cases where brain metastasis (cancer that has spread to the brain) resisted treatment by radiotherapy.

Thanks to the support of you, our Curestarters, Dr Valiente was able to discover how the activation of a specific receptor in the brain triggers this resistance to radiotherapy.

Incredibly, he and his team found that a drug called a RAGE inhibitor, which works by blocking the activation of that receptor, could make brain metastases vulnerable to radiotherapy. Of the samples taken from patients' brain tumours that resisted treatment, 7 out of 7 were re-sensitised to radiotherapy using the drug.

This incredible effect seemed to be dependent on the specific microenvironment found in the brain, so the effect applied to brain metastases regardless of where the cancer had originally started. That means it has the potential to help many patients.

Dr Manuel Valiente, Worldwide Cancer Research, lead author of the study
“It’s really amazing how quickly the results have translated to the clinic. It’s probably the only time this may happen in my whole life. It’s really great to have this feeling!”

Remarkably, this ground-breaking research that you supported will soon have a direct impact on patients. This often takes years, but Dr Valiente’s findings have already led to a new clinical trial which is due to launch this year.

The trial will recruit patients who have recently been diagnosed with glioblastoma, an aggressive type of brain cancer. It will test if combining radiotherapy and chemotherapy (temozolomide) with a RAGE inhibitor (azeliragon) is safe for use, and if it prevents the brain tumour resisting the effects of radiotherapy.

Alongside this, a sister study will see if it is possible to predict which patients will benefit from radiotherapy before they receive treatment. The researchers plan to test 200 patients with brain metastasis for a protein called S100A9, which is linked to radiotherapy resistance, then follow them over the next two years to see who responds to see who does or doesn’t respond well to treatment.

Image caption: Microscopic image of a mouse brain, metastatic cancer cells shown in green

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Hope for the future

The news of this exciting clinical trial gives us hope that more patients could live longer lives after being diagnosed with brain tumours. Sadly, there are currently few treatments that work well after cancer has spread to the brain.

Anne’s daughter Cathrin was just 34 when she was diagnosed with aggressive breast cancer. Devastatingly, the cancer spread to other parts of Cathrin’s body, including her brain, and neither surgery nor radiotherapy worked.

Cathrin sadly passed away in May 2020. Today, Anne and her family live in hope that cancer research will find new, effective treatments for people whose cancer has spread to the brain – treatments that are desperately needed so that other families don’t have to suffer the same loss.

On hearing the news of the trial, Anne said:

"When we were told the awful news that my daughter Cathrin’s breast cancer had spread to her brain, we were shocked to learn how few treatments work at that stage of the disease. Devastatingly, she passed away at just 38.

"Learning that Worldwide Cancer Research was funding Dr Valiente’s project gave me a glimmer of hope that new treatments might soon be possible, and it’s truly incredible to see that work already paying off. It’s so important that people donate to research like this because it’s the only thing that will stop more families like mine from experiencing the pain that we’ve felt."

We are so grateful for the support of our Curestarters for making breakthroughs like this possible.

With your generosity, we can support brilliant new ideas for cancer cures, just like Dr Valiente’s, and look forward to a future where more patients can receive the help they need.

Close up of a smiling scientist

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