Glioblastomas may be fuelled by overactive mitochondria

Existing drugs could treat as many as one in five glioblastomas, a new study has found.

Glioblastomas are the most common primary brain cancer in adults, with an average survival time of 15 months. Current research based on genetic classification of these cancers has so far yielded little improvement to this prognosis. Building on previous attempts to categorise glioblastomas, the researchers at Columbia University, New York used metabolic analysis to shed new light on what helps these cancers grow. Not only does this work show what makes these cancers so aggressive, but also that some may be effectively treated with drugs already in development.

'Existing classifications for brain cancer are not informative. They don't predict outcomes; they don't tell us which treatments will work best,' said Dr Anna Lasorella, who led the research. Professor Antonio Iavorone, co-lead of the study, added: 'We feel that one of the reasons therapeutic progress in brain cancer has been so slow is because we don't have a good way to classify these tumours.'

The study, published in Nature Cancer, used single-cell analysis technology to look at the underlying biological processes in 17,367 individual cells from 36 different tumours. Using computational analysis, the scientists were able to define four categories of glioblastoma based on their core cellular functions.

Professor Iavarone explained: 'In this way, we can classify each individual tumour cell based on the real biology that sustains them.'

One of these categories, which the researchers termed 'mitochondrial glioblastomas', is fuelled by the energy generated by overactive mitochondria. The team found that this activity could be dampened using mitochondrial inhibitors currently in clinical trials, slowing the growth of these cancer cells.

'We can now expand these clinical trials to a much larger group of patients, because we can identify patients with mitochondria-driven tumours, regardless of the underlying genetics,' explained Professor Iavorone.

While the mitochondrial group already shows some promise of possible treatment, the discovery of the other three categories offers hope for the treatment of more cases of glioblastoma. The researchers are also applying this principle to a broader range of tumours, in the hope that they may reveal previously unnoticed similarities. This could allow successful treatments to be used to treat different cancers with similar metabolic characteristics.

'When we classify based on the cell's core biological activities, which all cells rely on to survive and thrive, we may find that cancers share more in common than was previously apparent by just looking at their genes,' said Dr Lasorella.