Nanoparticles shed by cancer cells into the bloodstream could become a new tool for making more precise diagnoses and tailoring the treatment of people with brain cancer. The method could identify tumours more accurately in a minimally invasive way while also enabling doctors to monitor how the disease develops over time, says a researcher.
Glioblastoma is the most aggressive form of primary brain cancer, and the outlook remains extremely poor.
Five years after diagnosis, only 6.8% of patients are still alive, and the typical patient survives for just 12–18 months.
A new study now suggests that a blood test could give doctors something they currently lack: the ability to monitor the disease throughout a course of treatment.
The method involves isolating extracellular vesicles from a patient’s blood and analysing the molecules that cancer cells have packed inside them. The vesicles act as tiny packets of information that are released from cells and circulate throughout the body.
“Extracellular vesicles are tiny nanoparticles that our cells release into bodily fluids. They carry traces of what is happening inside the cells, which is why we can use them to track the progression of disease in real time. This property makes them unique as a tool for monitoring glioblastoma over time,” explains a researcher behind the study, Vineesh Indira Chandran, Assistant Professor at the Department of Clinical Medicine at Aarhus University in Denmark.
The research has been published in NPJ Precision Oncology, Brain and Clinical Cancer Research.
A blood test could spare some patients brain biopsies
Currently, doctors may need to open the skull and take a tissue sample from the tumour itself to determine the tumour type and which treatment is most likely to be effective.
However, this invasive procedure can lead to bleeding, infection and leakage of cerebrospinal fluid – the fluid that surrounds the brain and spinal cord. In some patients, the tumour is also difficult or impossible to reach safely with a biopsy.
A tissue sample also provides only a static snapshot of a tumour that can change significantly during the progression of the disease. This means that the most aggressive parts of the cancer may be missed.
In addition, determining whether a treatment is working or whether the disease is continuing to progress can be difficult.
Magnetic resonance imaging (MRI) cannot always distinguish between true disease progression and pseudoprogression, in which a tumour appears to be growing on the scan without actually doing so. In some studies, the error rate has been reported to be as high as 30%.
“When we use invasive diagnostic techniques, they present a range of surgical risks that we avoid when we analyse vesicles in the blood instead. Further, a tissue sample is difficult to repeat throughout a course of treatment, whereas blood samples can be taken at multiple time points to see how the tumour is changing,” says Vineesh Indira Chandran.
A single molecule provided the first clue
In a previous study, Vineesh Indira Chandran and colleagues showed that levels of the protein syndecan-1 on extracellular vesicles in blood plasma can distinguish patients with glioblastoma from patients with less aggressive forms of glioma.
The analysis distinguished between the groups with high accuracy.
The study also showed that syndecan-1 could reveal how much tumour remained after surgery. This raised the possibility that the vesicles could be used for more than diagnosis alone.
These findings are highlighted in the new review, which brings together results from a wide range of studies. Across the field, the same picture is emerging: extracellular vesicles could become an important tool for monitoring glioblastoma through blood tests.
“In the earlier study, we looked at extracellular vesicle-associated syndecan-1 alone. We showed that the level of this single molecule on the vesicles can distinguish a patient with aggressive glioblastoma from a patient with a less aggressive form of the disease. That was the first clear sign that the method could work, and we are now building on that finding,” explains Vineesh Indira Chandran.
Now the hard work begins
However, a single molecule such as syndecan-1 cannot capture the full complexity of glioblastoma. Different parts of the same tumour can be biologically distinct.
The next step is therefore to combine multiple markers from the vesicles rather than relying on a single molecule.
Such a panel could both identify the type of glioblastoma a patient has and reveal how the tumour responds to treatment over time.
“A single molecule will not be able to provide a comprehensive representation of the tumour’s complexity. We need to look at a combination of several molecules if we are to obtain a sufficiently accurate picture of how the disease is progressing. This is one of the next important milestones in our work,” says Vineesh Indira Chandran.
The goal is to follow the tumour through a blood sample
The technology must now be tested in larger groups of patients before it can be used in hospitals. Similar blood tests for patients with glioblastoma are being developed in several places around the world.
Vineesh Indira Chandran’s research group is taking part in a multicentre biomarker study involving more than 500 patients in India and Slovenia.
The vesicles are also attracting interest in many other diseases because they are released by virtually all the body’s cells and can therefore reveal signs of a wide range of conditions.
They are being investigated as diagnostic tools for Alzheimer’s disease, Parkinson’s disease and many types of cancer in addition to glioblastoma.
“Clinical validation is absolutely crucial before we can use extracellular vesicles to help guide treatment for individual patients. If all goes well, we could be around five years away from seeing the first clinical applications, and perhaps even sooner,” concludes Vineesh Indira Chandran.
