Meningioma is the most common primary brain tumour that occurs within the skull and spine.
Tumour suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumour suppressor genes don't work properly, cells can grow out of control, and this can lead to cancer. Merlin is a tumour suppressor protein that is frequently mutated (changed in form or nature) in meningioma.
The research team at our University of Plymouth centre have identified cellular activity and pathways that are upregulated (the process of increasing the response to a stimulus) in Merlin-deficient tumours and which consequently contribute to tumour growth.
Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma.
They used tissue and cells derived from meningioma tumours to investigate the expression of the protein DCAF part of an enzyme call E3 ubiquitin ligase, which regulates protein breakdown and other cellular functions, and confirmed it, and other proteins, were produced in abnormally large amounts in their samples.
They then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor – this affects activity of the E3 ubiquitin ligase - alongside a further inhibitor and found this affected tumour activity to a greater extent than either treatment used in isolation.
This research activity therefore represents an attractive novel strategy in the treatment of Merlin-deficient meningioma.
The Takeda Pharmaceutical Company Limited is a Japanese multinational pharmaceutical and biopharmaceutical company. It is the largest pharmaceutical company in Asia and one of the top 20 largest pharmaceutical companies in the world by revenue. Just before this encouraging research was reported in a top 5 % journal the pharmaceutical company Takeda who manufacture MLN3651 have unfortunately stopped its production.
Although this could be seen as a setback the knowledge gained won’t be lost but taken forward in new settings.
Our patron supermodel, actress, entrepreneur and mother Caprice Bourret commented on this research news
“I am so pleased to hear these research updates from Plymouth – it is a centre I have visited and I was so impressed by the dedication of Professor Hanemann and his team. The sustainable funding, we have provided to Plymouth for over five years is clearly the way forward in our fight to improve the outlook for people diagnosed with all types of brain tumour, including Meningioma”
Caprice became a part of the Brain Tumour Research family following her own meningioma diagnosis, and subsequent successful surgical intervention, in Spring 2017.
We are very pleased that the sustainable funding we have supported the work of Professor Hanemann with for over five years, and which we will continue to do so, has delivered another promising research paper – a clear example that our centre model is the way forward in the search for progress and improvements in patient options and outcomes.
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