Research into Childhood Brain Stem Glioma Treatment

VU University Medical Center Amsterdam Research

The Semmy Foundation supports research into childhood brain stem glioma treatment at VU University Medical Center Amsterdam (VUmc). This is especially important. Today’s discoveries, tomorrow’s cures. Innovative research has resulted in survival rates for childhood leukemia increasing from less than 10% in the 1960’s to more than 80% today.

Children suffering from brain stem glioma deserve at least a chance of survival too. This is the goal of the research team, led by Prof. Gertjan Kaspers.


Different Research Methods

The team is engaged in laboratory research and clinical research. Real innovation originates in the laboratory. Researchers study the properties of the cancer cells and test all kinds of new treatments for reducing the spread of cancer cells.

Clinical testing is used to trial promising treatments. Unfortunately treatment is often less effective when tried on a patient than in the lab and can produce unexpected side-effects, some of which can be very serious. Clinical trials cannot be carried out on adults since this type of cancer does not occur in adults. Children are not small versions of adults. They can react very differently to a particular treatment.

Laboratory Research and the Results

  • The laboratory research team needs samples for testing. This can be tumor cells (cell lines) or mice with brain stem glioma (mouse model). So far, the research team has generated one cell line from tumor cells obtained from a post mortem. However, the genetic material (DNA) in the tumors was more closely matched to that of mice than of humans. Other research teams around the world have encountered the same thing. Studies are being conducted to find out how this is possible. Recently a new mouse model was created from another post mortem and this time it probably is a “human tumor”. This could be very significant but more testing is required before this can be confirmed.
  • The VUmc team collaborates with various partners globally, for example in America and Spain, in order to obtain more research material. The researchers also try to create mouse models from the cells from abroad.
  • The creation of a mouse model involves injecting tumor cells into the brains of healthy mice. Tests are trying to modify the material before it is injected: a gene is added which makes the tumor cells emit light. That light should be visible on photographs taken on a special CCD camera. This enables the team to track the growth of the tumor cells.
  • A cell in the body can become cancerous if the cell DNA sends a signal to grow quickly. A study recently discovered that 70 to 80% of children with brain stem glioma have an abnormality in the DNA of the cancer cells (in the Histone H3 gene). Around the world, researchers are trying to develop a cure that will repair this abnormality or that will counteract its effects (cellular growth). The team at VUmc is also working on this.
  • Cellular growth can also occur if substances around the cancer cell send a signal. These substances are known as growth factors. The VUmc team is looking for a drug that will block these signals and prevent the growth. So far, sixteen drugs have been tested on cells taken from 6 different patients. A few appear to stop the signals and will be studied further. The team discovered that tumor cells save themselves when they are blocked by a drug. They do this by taking “alternative pathways”: if one pathway is blocked off, then the cells use another in order to continue growing. This may mean that tumors cannot be treated using only one drug. Rather several drugs are needed that each work on a different growth pathway.
  • Our generic material is folded into every cell of our body, including cancer cells. Certain proteins are responsible for the folds. If it is not folded properly, the genetic material functions differently. In children with brain stem glioma the folds appear to be disrupted. The team is researching drugs that can repair the folds.
  • The researchers use mice for testing drugs and for testing a new technique for delivering those drugs. This technique is known as convection enhanced delivery (CED). CED involves the insertion of a needle into the tumor. This allows the drug to be delivered directly into the tumor instead of via an artery. This means the protective layer between the blood and the brain cannot intercept the drug. Different studies found the use of the needle to be safe but that the technique does not work for every drug. The team is now researching which drug is most suitable for CED and if the drugs work better when this technique is employed. The VUmc research team are investigating the possibility of offering CED treatment to patients in the hospital. This must first be approved by an “ethics committee”, which decides if a treatment is safe enough for patients.

Testing on Hospital Patients and the Results

  • Children with brain stem glioma can undergo experimental therapy at VUmc. This means that the therapy has not yet been proven to work, although laboratory research has already shown that the drugs being used can potentially stop the tumor growth. The experimental therapy is monitored to check if the drug works in the patient’s body and if it is safe. At this stage it is impossible to say if the therapy works, too few patients have undergone the therapy. Most patients are able to cope well with the treatment and do not experience too may side-effects.
  • One study has been completed which resulted in the drug Bevacizumab (Avastin) being marked as radioactive. The drug was delivered via the patient’s artery and a PET scan was used to track its progress through the body. The scan should show if the drug manages to reach the tumor but also if it goes to other areas of the body such as the liver, kidneys, bones, etc where it could cause side-effects. Seven patients were scanned in total. In five out the seven patients Bevacizumab did reach the tumor but there were substantial differences in the amounts. These results are very significant. It may enable doctors to predict which patients will benefit from a particular drug and which will only experience side-effects. The VUmc will soon begin a new PET study with other drugs.
  • During post-mortem studies on children who have dies from brain stem glioma the tumor is removed and healthy brain tissue samples are taken. These will be used for laboratory studies. Ten post-mortems have been performed so far. None of the parents had any regrets that they gave permission for these studies. The post-mortem results are extremely useful for laboratory research.
  • The VUmc research team is also participating is a new study using patient information from all over Europe. Fifteen European and two non-European countries together established a network for children with brain stem glioma: the SOPE-DIPG Registry. VUmc took the lead and coordinated the creation of the Registry. The database is administered from the Netherlands. The aim of the network is to collect and compare the (treatment) results and MRI-scans of all patients in Europe. Hopefully this can help shed some light on the possible causes of brain stem tumors. It should also make it easier to compare the effectiveness of different therapies.


Further Information on the Research and Results: