New medulloblastoma research, what’s going on at the NCI, the origins of GBM plus trials and industry news

Brain Tumour Research

2 min read

We start with research into how a specific gene fuels a deadly Group 3 medulloblastoma.

The gene is OTX2 and it acts like a control switch but researchers have discovered that this control switch is dysfunctional, and it keeps the cancer stem cells in a permanently ‘on’ position so that the OTX2 gene is perpetually fuelling the medulloblastoma.

Researchers then mimicked the effects of decreasing OTX2 with drugs and found targeting this pathway and silencing the OTX2 gene dramatically decreased tumour growth.

One study scientist commented, “Understanding how control switches like OTX2 help make medulloblastomas grow offers fresh opportunities to target Group 3 medulloblastoma, prevent progression and spread and decrease the toxicity of therapy for children with this devastating disease.”

In clinical trials news, the first patient has been dosed and continues on therapy in a trial assessing bemcentinib in recurrent glioblastoma.

The study will enrol up to 20 recurrent GBM patients, at up to 15 sites in the USA. 10 patients will be treated prior to surgery and 10 patients will have no pre-surgical treatment. However, all patients will receive treatment with bemcentinib following surgery.

The endpoints (the outcomes to be reported on) of the study include an evaluation of bemcentinib’s ability to cross the blood-brain barrier, AXL expression (Increased expression of AXL is significantly linked with poor prognosis in GBM patients), pharmacokinetics ( what the body does to the drug), safety and tolerability, as well as efficacy assessments including progression-free survival and overall survival.

This trial is funded by the NCI and last year I had the huge honour of visiting the NCI Neuro-Oncology Branch at the National Institutes of Health (NIH) in Bethesda, Maryland. Here are recent updates on some of the work they are currently undertaking as reported on their Twitter account (@NIHBrainTumor) this week; Immunotherapy in CNS cancers: the role of immune cell trafficking, MGMT Status as a Clinical Biomarker in Glioblastoma & How Glioblastoma cells can undergo exploratory adaptation to survive and cause recurrence

Industry news now as the first patient is enrolled in Novocure’s EF-33 Phase 2 Pilot Trial of Tumour Treating Fields delivered utilizing high-intensity transducer arrays

More medulloblastoma news as Brazilian researchers demonstrate the potential of leukaemia drug, arsenic trioxide, to treat medulloblastoma. There were promising results not only in terms of cell death but also making the tumour cells more sensitive to radiation therapy.

Finally this week Glioblastoma - does this malign cancer originate from a pool of stem cells that can be a significant distance away from the resulting tumours?

Unlike many cancers, which start out as low-grade tumours that are more treatable when they're caught at an early stage, most glioblastomas are almost universally discovered as high-grade and aggressive lesions that are difficult to treat with the currently available interventions (mainly surgery, radiation and chemotherapy).

Sadly, once a GBM patient has neurological symptoms like headache, nausea, and vomiting, the tumour is already at an end state, and disease progression is often very rapid. We know that the earlier you catch and treat cancers, the better the prognosis will be, but with GBM there's no way to catch the disease early.

However, this recent research in glioblastoma patients shows that the subventricular zone (SVZ) -- an area that is the largest source of stem cells in the adult brain -- contains cells with cancer-driving mutations that are shared with tumours found in other often far-distant brain regions.

Click on the hyperlink above to find out more about this fascinating research but there is no doubt that the more we learn about glioblastoma the more hope we can give to these patients who currently have few effective options.

That is why we fund GBM research at The Brain Tumour Research Centre at Queen Mary University of London (QMUL) led by the inspirational Professor Silvia Marino.