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Glioblastoma — the most common and deadliest form of brain cancer — strikes up to 300 Danes every year. They receive surgery, radiotherapy and chemotherapy, but these treatments come at a cost to quality of life, and sooner or later patients relapse and die from the disease. 

That is why consultant neurosurgeon Anders Rosendal Korshøj at the Department of Neurosurgery at Aarhus University Hospital wants to test two drugs in a large clinical trial — drugs that in combination could potentially extend patients' lives. 

"The goal is to give patients a significantly longer survival without compromising their quality of life," he says. 

On receiving the Lundbeck Foundation grant, he says: 

"I am proud of the recognition that such a grant represents, but above all I am pleased to get started on a project that has been in the making for two to three years. If it succeeds, it will be a long-awaited breakthrough — there have been no advances in the treatment of this disease for decades." 

The ambition is for patients at all hospitals in the country who have recently received the diagnosis to be offered the opportunity to participate in the trial. During surgery to remove the tumour, the surgeons will take tissue samples. But beyond the standard tissue analysis, the samples will undergo various advanced analyses carried out by experts at Anders Rosendal Korshøj's own laboratory and at other laboratories. These analyses will allow researchers to describe the disease mechanisms in detail and potentially identify who will benefit most — and least — from the treatment. 

After surgery, half the patients will be randomly assigned to receive the two drugs alongside radiotherapy and chemotherapy. Beyond the effect on the disease itself, the researchers expect a synergistic effect, as one of the drugs has been shown in mouse studies to also enhance the effect of radiotherapy and chemotherapy. 

Approximately 20 per cent of patients will require a second operation when the disease relapses, and at that point doctors will again take tissue samples to reveal how the disease has escaped the treatment effect. 

The final outcome of the trial will be determined when researchers can compare the survival and time to relapse in patients who received the drugs against those who did not. 

The goal with the two drugs is to target two different mechanisms discovered by the recipients of the Lundbeck Foundation's Brain Prize last year: Professor Michelle Monje from Stanford University, USA, and Professor Frank Winkler from Heidelberg University. 

Michelle Monje discovered that normal brain cells send signals to all cells in the brain telling them to grow — and this includes cancer cells. Anders Rosendal Korshøj will intervene in this mechanism using an approved epilepsy drug that has been shown in mouse studies to inhibit communication between brain cells and cancer cells, thereby extending the animals' survival. 

Frank Winkler — with whom Anders Rosendal Korshøj collaborates — discovered that cancer cells, like other cells in the brain, communicate via networks. And within the cancer cell networks there are special cells that maintain a constant rhythmic activity. When these cells die, the entire network dies with them. The researchers will target these cells with a compound that has not yet been approved but has previously been approved for human trials. In mouse studies, it has been shown to disable cancer cell networks. 

"By targeting the two different mechanisms at the same time, we have a greater chance of halting the disease," says Anders Rosendal Korshøj.