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Lack of one signaling protein curtails brain tumor growth, Stanford study finds

Over the last decade, Stanford neuro-oncologist Michelle Monje, MD, PhD, and her team have been making steady progress in understanding the inner workings of an extremely deadly childhood brain tumor. Called diffuse intrinsic pontine glioma, the tumor strikes school-aged children and has a tragically low five-year survival rate of around one percent. DIPG is one of a group of aggressive brain tumors called high-grade gliomas that share important aspects of their biology.

Today in Nature, Monje and her colleagues report the latest development in their research: They have discovered that lack of a specific signaling protein in the brain dramatically halts growth of tumors in this group.

The protein, neuroligin-3, normally helps signal formation and activity of synapses. In 2015, Monje's team discovered that high-grade gliomas hijack the protein's normal function to help drive their growth.

The new study went a step further, testing what happened when human glioma tissue was implanted in the brains of mice that had been genetically engineered to lack neuroligin-3. Monje explains in our press release:

We thought that when we put glioma cells into a mouse brain that was neuroligin-3 deficient, that might decrease tumor growth to some measurable extent. What we found was really startling to us: For several months, these brain tumors simply didn’t grow.

The effect was specific to high-grade gliomas, and after 4 1/2 months of completely stagnated growth, some of the tumors began to grow again, the team observed.

The researchers also tested two chemical inhibitors of neuroligin-3 secretion in mice implanted with human tumors whose brains could manufacture neuroligin-3 normally. The inhibitors, one of which has reached phase two clinical trials for another form of cancer, dramatically halted the tumors' spread over a short period.

The new findings don't represent a cure for high-grade gliomas, but could be an important piece of a larger strategy to tackle these hard-to-cure cancers. Again, from our release:

'We will have to attack these tumors from many different angles to cure them,' Monje said. But given how devastating the tumors are, the possibility of using neuroligin-3 inhibition to slow tumor progression is a hopeful development, she added. 'Any measurable extension of life and improvement of quality of life is a real win for these patients.'

Previously: A tumor donation yields answers for a devastating form of childhood cancer, Moving toward multi-pronged treatment for the worst childhood brain tumor and Brain tumor growth driven by neuronal activity, Stanford-led study finds  
Photo by wyinoue

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