Bright solution to treating inaccessible brain tumours
Some forms of brain cancer, such as glioblastoma multiforme (GBM), are all too often inoperable. This is because they are deep lying, hard to access, and extremely aggressive. Current brain cancer treatments simply cannot reach GBM tumours without risky and highly invasive open surgery. “GBM is incurable, progresses fast, and is terminal,” notes Lumiblast project team member Theodossis Theodossiou from Oslo University Hospital in Norway. “A solution to this disease is clearly needed in clinical settings.”
Challenges of photodynamic therapies
Conventional cancer treatments include photodynamic therapy (PDT). This involves delivering drugs to tumour areas that make cells sensitive to light. When an external light is shone onto the tumour, the combination of the drug and the light destroys the cancer cells. However, PDT treatments cannot take care of surrounding diseased tissue. The location of GBM tumours also still often requires open surgery, because external light cannot penetrate deeply enough or through the skull. The idea for a novel GBM treatment came out of a conversation between future project partners. “I was discussing with Georgios Vougioukalakis from the National and Kapodistrian University of Athens whether it would be possible to make luminescent compounds that accumulate in cell mitochondria,” explains Theodossiou. “His answer was ‘yes’, and this was the basis for the Lumiblast project.”
Chemiluminescent compounds that target tumour cells
The project had to be built up from the ground, because the technology being proposed was so cutting edge. “There has been nothing like this before,” says Theodossiou. “We are talking about chemiluminescent compounds that produce self-sustained light within cancer cells.” To begin, Vougioukalakis’ team began developing prospective chemiluminescent compounds. These were then sent to Oslo University Hospital to be tested in cells. The photophysical properties of the compounds were investigated by Valencia Polytechnic University in Spain, with the two other partners being Knight Scientific in the United Kingdom and the University of Oslo. “We screened many compounds,” notes Theodossiou. “Our goal was to develop a library of compounds and to see which ones could do the job. After a lot of screening, we found a couple that worked, one of which worked particularly well.” Later in the project, Theodossiou and his team applied compounds to tumours in vivo. “This was not the ideal setting as the tumours were not in the brain, but is a necessary first step,” he adds. “These tests showed a clear improvement in inhibiting the growth of tumours with Lumiblast technology.”
New approach to treating brain cancer
The success of Lumiblast has the potential to transform brain cancer treatment. Because the photons are produced inside the cancer cells themselves, invasive surgery is not needed to access and shine a light on these difficult-to-access tumours. Instead, each GBM cell becomes a small ‘lamp’, providing the light required for photosensitive agents to become activated and kill them from their own insides. “We are currently seeking new funding in order to build on this project and make Lumiblast a viable clinical technology,” remarks Theodossiou. “We need to develop biocompatible formulations and validate its effectiveness in orthotopic GBM models; these are the two key aims moving forward.” One reason the team is so keen to move forward quickly is because they believe that the potential for an effective treatment is there. “We started this project with the ambitious vision of curing GBM,” says Theodossiou. “We believe we are on the right path, and that we can ultimately achieve this.”
Keywords
Lumiblast, brain, cancer, tumour, GBM, chemiluminescent, surgery, PDT
