Glioblastoma research: why we need smarter methods to fight brain tumours
About a year ago, I walked out of my house and realised that something was wrong at my neighbour’s place. Pascal had been going through a hard time over the past months because his tumour had come back. Sadly, that day was Pascal’s last.
The tumour that took Pascal’s life is the most frequent and aggressive form of brain tumour, called glioblastoma. Despite the situation, Pascal had been somewhat lucky, enjoying about 8 years of good life after a dreadful initial diagnosis. Then things got awry again. Pascal knew I was involved in glioblastoma research. Each time we’d see each other, he’d ask me: “So, Gauthier, did you find anything for me?” The honest answer was a heartbreaking “Not yet, I’m sorry Pascal”.
Jumping in the glioblastoma unknown
My journey in glioblastoma research started in 2013, when we received a request to fund a trial testing what many thought was a crazy idea: using 10 drugs together against recurrent glioblastoma to hinder its growth. This was just a concept, but we liked it. Bold ideas are needed against unmerciful diseases. My colleague Kristine and I helped the team develop the clinical trial, which we then funded. The results came out a few years later with encouraging data: the 10-drug combination was well-tolerated and 3 out of 10 patients survived for several years.
The trial was a success, but there was a problem. No one outside the trial team thought it made sense to throw ‘10 spaghetti at the wall’ hoping some would stick, without any clue which one(s) did and why . The opposite of being precise, at a time when precision oncology was booming. Consequently, the next trial hasn’t happened.
Knowledge about brain tumours is not enough
Since 2013, the amount of knowledge generated about the biology of glioblastoma has been as impressive as the lack of progress in treating patients affected by the disease. Knowledge hasn’t translated into any major improvement. Pascal obviously couldn’t accept that. When attempting to explain it to him, I realised I was just finding excuses after all. I could read his mind: if you think you know why it keeps failing, then address the problems.
Remarkably, progress since 2013 has come from improvement in research methods, not from brand new, ‘sexy’ drugs. Anyone sufficiently exposed to glioblastoma research knows that the vast majority of novel drugs hit the glioblastoma wall, one after another. The issue comes, at least partly, from the inefficient research methods we have been using.
Being ‘brainy’ to make progress against brain tumours
Among the solutions put forward, I find two of them truly transformative: accelerating the pace of drug testing and ensuring drugs actually reach the tumour.
- Accelerating the pace via platform trials
A typical clinical trial in glioblastoma will take 5 to 10 years from concept to results. If done one after another, researchers may be able to contribute to 4-5 trials over their entire career. Platform trials testing multiple drugs within the same protocol emerged as a way to accelerate that pace.
For example, GBM Agile, a US initiative, has reported three (negative) results over 7 years, and 5 other interventions are being tested or lined up.
MAGMA, an Australian initiative, asked two important yet simple questions about optimising the use of the only effective drug we have, and got an answer in a record time during the pandemic.
The German N2M2 also accelerated the pace of testing precision research questions in glioblastoma. As a trial funder, I don’t think we should ever support any traditional trial that will take 10 years to report results (likely negative) but rather ‘demand’ that our funding goes to glioblastoma platform trials only.
- Outsmarting the blood-brain barrier
A brain tumour is protected by the blood-brain barrier, a natural defence mechanism. This protection holds against most medicines. Drug substances don’t get to the brain after an oral or intravenous administration, with few exceptions. Historically, many brain tumour researchers haven’t cared too much, stating that the blood-brain barrier is likely disrupted in patients. Many now believe not paying attention to this issue is exactly why we hit the wall. One solution is to only use drugs already known to reach the brain (e.g. psychoactive drugs) or to check directly whether the drugs entered the tumour.
Doing our bit against brain tumours, thanks to patients, families and … Europe
At Anticancer Fund, we have decided to provide support to both types of efforts. First, we selected and funded EViDENCE-BM, a trial testing whether drugs known to pass the blood-brain barrier are active against the specific brain metastases of each patient. Second, and thanks to our accumulated knowledge and experience in drug repurposing, we are now involved in EPIC GB, an ambitious 5-year project funded by Yorkshire Cancer Research, that aims to test if drugs do get into the tumour tissue.
Though our foundation is not entirely dedicated to brain tumours, we know that the needs are massive for the patients and families affected. We are doing our utmost best to make progress against brain tumours. Very recently, I was truly enthused and energised by the strong messages coming out of an event on brain tumour research hosted by Sophie Wilmès, Member of the European Parliament, with strong support from the European Commission President Ursula von der Leyen. I’m hopeful that we’re on to something with the projects we support.
A call to action
I hope that what we have learned can help other funders and individuals decide where they can contribute:
- First, improvement in research methods is instrumental. We cannot accept a slow pace of throwing spaghetti at the wall.
- Second, as Antoine, a friend of a friend who recently lost his young wife, says, the drive of patients and families affected by this disease fuels everyone’s energy to keep going against glioblastoma.
Please continue pushing us, providing that sense of urgency, and getting involved in research projects. We need you. You need us. Let’s do it together.
