Scientists discover a chemical that can kill glioblastoma cells

Thursday 16 August 2018

Laboratory experiments show that a synthetic chemical is able to shut off glioblastoma cells' energy source, leading to cell death

All cells, including cancer cells, require energy to survive and grow, which they get through the metabolic breakdown of nutrients. Mitochondria are small structures within cells that regulate cell metabolism and function as energy-generating factories.

New research published in Science Translational Medicine reveals that a chemical called KHS101 is able to disrupt the activity of mitochondria and thereby shut off the tumour cells' source of energy.

Dr Heiko Wurdak, from the University of Leeds who led the international research team, said: “When we started this research we thought KHS101 might slow down the growth of glioblastoma, but we were surprised to find that the tumour cells basically self-destructed when exposed to it.

“This is the first step in a long process, but our findings pave the way for drug developers to start investigating the uses of this chemical, and we hope that one day it will be helping to extend people's lives in the clinic."

Glioblastomas are the most common high-grade and aggressive primary brain tumour in adults, with a five-year survival rate of less than­ five per cent.

The findings from this study highlight the potential for using KHS101-like chemicals to treat cancers such as glioblastoma, and could be the first step in developing new ways to tackle this devastating disease.

The blood-brain barrier is a layer of tightly-connected cells lining the inner surface of the blood vessels that feed the brain.

It's the brain's way of protecting itself from harmful agents and toxic materials, while letting oxygen and nutrients in and waste products out. Because the blood-brain barrier stops most molecules from entering the brain, it represents one of the most difficult challenges when developing treatments for brain tumours.

To test whether KHS101 could cross the blood-brain barrier in mammals, researchers transferred glioblastoma tumour cells from humans into mice.

The results showed that KHS101 successfully crossed the blood-brain barrier and significantly decreased tumour growth (by around 50%) in mice treated with the chemical compared with those given a placebo, leading to an increase in survival. Importantly, normal brain cells were unaffected by the chemical.

The team also reviewed how effective KHS101 would be against the different genetic profiles of cells within a tumour, and between tumours in different patients.

Genetic variation in tumours has complicated efforts to identify treatments in the past, but the team found that all tested variations of glioblastoma subtype cells responded to the treatment.

Professor Richard Gilbertson, Cancer Research UK's brain tumour expert said: “Treatment for glioblastoma has remained essentially unchanged for decades, so there is a pressing need for preclinical research like this to identify and characterise potential new drugs.

“While the findings are encouraging, as an experimental chemical, further rigorous testing and refinement of KHS101 is required before trials in people can begin."

Further research into the properties of KHS101 may lead scientists to discover similar drugs that can disturb the energy sources, causing self-destruction of tumour cells, and thus broaden the range of treatment options available in the fight against brain tumours.

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