Tuesday February 18 2014
Brain tumours can be hard to treat
“Cancer ‘monorails’ can be used to kill [brain] tumours by luring them into toxic pits or areas of the body that are safer to operate on,” BBC News reports.
This headline comes from an exciting new study which used thin tubes (termed ‘cancer guides’) to guide brain cancer cells away from the tumour to an area outside the brain.
Researchers made use of what is known as nanofibre technology. Nanofibres are tiny, less than 0.0001mm in width – a clump of 100 nanofibres would be around the same size as a single human hair.
The researchers conducted a number of experiments to create tubes to mimic nerve and blood vessels, the route by which brain cancers usually spread. Lining the tubes with nanofibres made cancer cells more likely to travel down them. They also studied the effects of the substance cyclopamine on causing brain tumour cell death without affecting other brain cells.
Rats were injected with human brain cancer cells 2mm beneath the skull. Seven days later the tubes were inserted next to the cancer and its cells went down the tubes. When the tubes led to an area outside the brain (which was described as “a sink”) containing cyclopamine, the cells died. The researchers also found that the size of the brain cancer reduced.
This is an encouraging new technique. Many human brain cancers are untreatable as the tumour cells are located in parts of the brain that cannot be safely reached using surgery or chemotherapy. So encouraging the cancer to “shift location” could lead to new treatment opportunities.
However, it is not known whether this method would cause all of the cancer to move or shrink and it did not assess survival rates.
Further animal studies will be required before any human trials can be conducted.
Where did the story come from?
The study was carried out by researchers from Georgia Institute of Technology, Emory University School of Medicine, Atlanta and the Children’s Health Care of Atlanta and was funded by the National Institutes of Health, the Georgia Research Alliance and Ian’s Friends Foundation.
The study was published in the peer-reviewed journal Nature Materials.
BBC News covered the study accurately, though using the image of a human scan perhaps implied the research was now at the human trial level.
The Mail Online’s coverage of the study was also accurate, though it chose to offer the metaphor of a “fishing rod reeling up” cancerous cell, rather than a “monorail”.
While these types of metaphors may seem fanciful to more specialised readers, they can be very useful in conveying complex ideas and concepts to people without scientific training.
What kind of research was this?
This was a laboratory study investigating a new technique which may be able to treat the most common type of primary aggressive brain tumour, called glioblastoma multiforme.
Current treatment options are surgery with or without radiotherapy and chemotherapy but prognosis is poor because the cancer has usually spread along nerves and blood vessels within the brain. This spread limits the ability to surgically remove all of it without damaging normal brain tissue.
This research aimed to see if a brain tumour could be guided to move outside of the brain so it could be destroyed, without causing damage to the brain.
What did the research involve?
The research involved laboratory studies to see if cancer cells would spread along manmade fibres leading to a substance that would cause the cells to die. The second part of the research used the technique in rats with a human brain tumour grafted into their brain, and monitored the effect on the cancer.
The researchers manufactured small tubes to mimic nerves and blood vessels of 2.4mm outer diameter which they described would act as a “tumour guide”.
The tubes were lined with a smooth film or nanofibres. They performed experiments in the laboratory to see if human cancer cells would move along these materials.
Studies were then conducted to test whether a substance called cyclopamine would cause cancer cell death. Cyclopamine comes from the corn lily that grows in the mountains of Nevada and California which is known to cause serious birth defects. The flower got its name after one-eyed lambs were born to sheep that grazed on it.
Research is ongoing for its potential role in treating a number of cancers, including multiple myeloma. Unlike other forms of chemotherapy, cyclopamine is only damaging to some types of cells.
They created a sac to hold the cyclopamine which was connected to the end of the tube. They then linked the cyclopamine to a collagen gel to see whether this would stop it from moving into surrounding tissues, and tested whether it still caused cancer cells to die.
The researchers then injected rats brains with cells of the human brain cancer, glioblastoma multiforme, 2mm under the skull surface. Seven days later when the cancer was growing, they inserted several types of tubes into the rat brains next to the cancer: empty tubes, tubes lined with smooth film, or tubes lined with the nanofibre. Some of the nanofibre tubes led to an area containing the cyclopamine linked to collagen gel (termed a ‘sink’).
The rats were euthanized after 18 days and their brains dissected.
What were the basic results?
In the laboratory studies:
- over 10 days, the cancer cells moved 1.5mm over the smooth film, but 4 to 4.5mm along the ‘aligned nanoparticle’ film.
- when human cancer cells and other brain cells were grown with 30µM cyclopamine, 80% of the cancer cells died, but none of the other types of brain cells died
- when cyclopamine was linked to the collagen gel it did not move into the surrounding tissues
In the rat studies:
- Cancer cells moved along all types of tubes, but more went along the tubes lined with the nanofibres.
- The cancer cells did not migrate on the outside of the tubes but were contained within them. The cancer cells did not die until they reached the cyclopamine at the end of the tubes in the sink.
- The total amount of brain cancer in the brain of the rats with the tubes lined with the nanofibres was statistically smaller than for the control (with no tube) or the empty tube. In rat brains where tubes with the nanofibre lining had been inserted, more tumour was in the tube and the amount of brain cancer left in the brain was statistically significantly smaller compared to the control.
- Rats with the empty tube inserted had the largest amount of total tumour compared to the control rats with no tubes and the rats with smooth lined and nanofibre lined tubes, and this was mostly in the brain.
How did the researchers interpret the results?
“The use of this technology for tumour cell migration, coupled to the cyclopamine-conjugated hydrogel sink, could potentially open new therapeutic approaches for management of brain cancers that are difficult to treat”. However they also acknowledged that “this study was not designed to evaluate the efficacy of the approach to affect survival”.
This is an exciting, novel technique that has been shown to reduce the size of a human brain cancer in rats and cause many of the cancer cells to move along a tube (‘cancer guide’) to an area where the substance cyclopamine caused their death. Early results do not show this substance is toxic to other brain cells or moves out of the sac into surrounding tissue.
A few points to consider include:
- Though the researchers measured the size of the remaining cancer, they did not report whether cancer cells had also started moving in other directions along vessels and nerves.
- It is not clear whether in longer studies the entire tumour would eventually move down these tubes.
- The tubes in question were only 6mm long – far longer tubes would be required for human brains.
- It is not clear why the empty tubes caused the cancer to grow more.
However, as the researchers and BBC news points out, it is early days and much more research will be required before any human studies can be conducted.
Analysis by Bazian. Edited by NHS Choices.
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