Cancer Research UK - Possible target for treating breast cancer that’s spread to brain found in mice
A molecule that could help tackle a certain type of breast cancer after it has spread to the brain has been identified in mice, according to a new study.
The research (link is external), published in Science Translational Medicine (link is external), suggests why drugs used to treat a certain type of breast cancer, called HER-2 positive breast cancer, that has spread to the brain, don’t work.
The researchers found that, in mice, breast cancer that spread to the brain was different to that which spread to other parts of the body. Tumours that went to the brain were unaffected by a drug that targets a certain set of molecules involved in tumour growth, while it shrank tumours in the rest of the body.
Dr Thomas Hughes (link is external), a Cancer Research UK-funded expert and associate Professor at the University of Leeds, said that this finding could be significant for a large number of patients. But he warned that, as this study was carried out in mice, any potential treatment would be years away.
“Once breast cancer has spread to the brain it almost always kills people, so any treatment that can tackle cancers that have spread is positive, as it’s likely to improve survival,” he added.
Around half of HER2-positive breast cancers will spread to the brain.
Dr Rakesh Jain, co-senior author of the report from Massachusetts General Hospital, said that this study shows that the different environments around the body can affect whether or not a drug works.
“This should be taken into account as new treatment approaches are developed," he said.
It was previously thought that drugs targeted against the tumour failed to enter the brain because they were too big to pass through an obstacle called the blood-brain barrier.
But the researchers showed that the drug reached the brain, meaning there was another reason why drugs weren’t shrinking the tumours.
The team looked for changes in the tumours of mice that might be stopping the drugs from working.
They found that a molecule called HER3 was present in high levels in the tumour, and tested drugs that targeted it.
HER3 is one of many molecules in a very complicated signalling network that affects the growth and survival of HER2-positive breast cancer cells.
One drug tested by the team blocks the HER3 molecule and the other stops the HER-2 and HER3 molecules interacting.
Giving the drugs alone did not slow the growth of the tumours in the brains of mice, but when used together with another drug called buparlisib the tumours started to shrink.
This drug combination also doubled survival in mice.
“The next step is to see if the same effects happen in people.” said Hughes.
Kodack, P. et al. (2017) The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation. Science Translational Medicine. DOI: 10.1126/scitranslmed.aal4682 (link is external)
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