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Chemical shows promise at killing glioblastoma cells in mouse studies

16 Aug 2018

Scientists have identified a synthetic chemical, named KHS101, which causes the death of aggressive brain tumour cells from patients in laboratory tests.

Published in Science Translational Medicine, the research shows early-stage progress towards developing new therapies for the brain cancer glioblastoma. Over 2,000 people are diagnosed with glioblastoma in the UK every year and it has a five-year survival rate of less than­ 5%.

The study, led by MRC-funded researchers at the University of Leeds, found that the synthetic chemical cut the energy source of glioblastoma tumour cells, leading to the cells’ death.

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.”

The study revealed that the chemical was disrupting the mitochondria and metabolism within the tumour cells, and shutting off the energy supply, leading to their self-destruction.

The researchers transferred human tumour cells into mice brains to test whether KHS101 could cross into a mammalian brain. The blood-brain barrier stops most molecules from entering the brain and severely limits treatment options for brain cancers.

The chemical successfully crossed the blood-brain barrier and significantly decreased tumour growth (by around 50%) in mice treated with KHS101 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.

Dr Nathan Richardson, the MRC’s Head of Molecular and Cellular Medicine, commented: “There is strong interest in dissecting the interplay between cancer and metabolism and preclinical studies like this are early but crucial steps towards developing new treatments for brain cancer. While these findings are promising, further testing is needed to establish safety and effectiveness before the compound can be studied in people.

“To drive new partnerships and discoveries in brain cancer research we are currently running a workshop for scientists in this field, in conjunction with the Brain Tumour Research charity and the British Neuroscience Association.”

The study was funded by the MRC, Brain Tumour Research, Support across Yorkshire, Worldwide Cancer Research, the European Commission (FP7), the Engineering and Physical Sciences Research Council, Cancer Research UK, and the Brain Tumour Charity.

This article is adapted from content supplied by the University of Leeds.

Categories

  • Categories: Research
  • Health categories: Cancer
  • Strategic objectives: Aim: Picking research that delivers
  • Locations: Other
  • Type: News article