Family of drugs used for treating muscular dystrophy could improve brain tumour treatment

Scientists from our Brain Tumour Research Centre of Excellence have led a new study into possible treatments for meningioma
Dr Juri Na, from the Brain Tumour Research Centre of Excellence at the ÌìÃÀ´«Ã½¹Ù·½ÍøÕ¾, and a Masters student conduct research in the labs at the Derriford Research Facility

Family of drugs used for treating muscular dystrophy could improve brain tumour treatment

Scientists from our Brain Tumour Research Centre of Excellence have led a new study into possible treatments for meningioma

A drug from the same family licensed for use in patients with Duchenne muscular dystrophy and blood cancer could transform the treatment of meningioma – the most common form of primary brain tumour in adults.
Scientists at the Brain Tumour Research Centre of Excellence at the ÌìÃÀ´«Ã½¹Ù·½ÍøÕ¾ carried out the research, using patient samples in the laboratory, and the results have been published in the journal Cell Death and Disease.
Around 3,500 adults are diagnosed with meningiomas each year and with no chemotherapy drugs proving effective, the main treatment is surgery. However, some people cannot have surgery safely due to the size or location of the tumour, and for those patients radiotherapy as the only treatment option. Unfortunately, in more aggressive forms of the disease, the tumour can become resistant to damage caused by radiotherapy, reducing its effectiveness.
As part of their ongoing work to uncover new treatment, the scientific team – led by Dr Juri Na and Professor Oliver Hanemann – explored whether a drug called dacinostat could help improve the impact of radiotherapy on meningioma.
Dacinostat belongs to a family of drugs known as HDAC (Histone Deacetylase) inhibitors, which affect how cells control their DNA and respond to damage. HDAC inhibitors have already shown promise in cancer therapy with three currently approved by the FDA for the treatment of various blood cancers and Duchenne muscular dystrophy.
Using patient samples to create models of meningioma in the laboratory, Dr Na and her team demonstrated that treating tumour cells with low doses of dacinostat before radiotherapy increased DNA damage and cell death, and reduced tumour growth.

For the first time, we show how dacinostat works in detail, revealing its potential as a new treatment for aggressive meningioma.

Outside surgery, these patients have very limited options, and radiotherapy alone is often insufficient for aggressive or recurrent meningiomas. This research provides strong evidence that combining radiotherapy with drugs such as dacinostat could improve tumour control while minimising treatment-related toxicity, with the potential to enhance patient quality of life.

Juri NaDr Juri Na
Senior Research Fellow

As well as identifying dacinostat as a potential route to boosting the effectiveness of radiotherapy, the team has uncovered for the first time the process that meningioma tumours use to repair DNA after radiotherapy. This has opened up a completely new area of research that could lead to more treatments to increase the effectiveness of radiotherapy.
Based on these findings, Dr Na and her team are now testing new treatment approaches that combine radiotherapy with approved anti-cancer drugs. After screening more than 7,000 drug combinations in meningioma models, they are now studying the most promising candidates in greater detail. The aim is to identify safe, effective combinations that can move rapidly into clinical use.
  • The full study – Shaji, Na and Hanemann: Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma – is published in Cell Death & Disease, DOI: .
 

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Dr Juri Na, from the Brain Tumour Research Centre of Excellence at the ÌìÃÀ´«Ã½¹Ù·½ÍøÕ¾, and a Masters student conduct research in the labs at the Derriford Research Facility

Brain Tumour Research Centre

The internationally renowned Brain Tumour Research Centre (BTRC) focuses on low-grade tumours and investigates new mechanisms underlying brain tumourigenesis, including tumour initiation. 
We work truly from bedside to bench and back. We have a large biobank of stratified tumour samples and are using a variety of complementary tumour models. The BTRC encompasses research groups working closely together and complementing each other with both shared approaches and shared in vitro and in vivo models.
 
Brain Tumour Research Centre of Excellence