The healing process that begins after a stroke, trauma, infection, or other brain injury can trigger the development of cancer, according to a study.
Canadian researchers analyzed cells from tumors from 26 patients with a common but aggressive form of brain tumor known as glioblastoma.
Their results suggest that mutations can derail the process that is supposed to create new cells to replace the lost ones – and fuel tumor growth.
The team hopes the discovery can pave the way for new tailored therapies for individual brain cancer patients.
The healing process that starts after a stroke or other type of brain injury can inadvertently trigger the development of cancer, according to a study. Pictured is a cross section of the brain with a glioblastoma tumor highlighted in pink
"Our data suggest that the correct mutation change in certain cells of the brain could be altered by injury to cause a tumor," said paper author and neurosurgeon Peter Dirks of the Toronto Hospital for Sick Children.
The results could lead to new therapies for glioblastoma patients who currently have limited treatment options and an average lifespan of only 15 months after diagnosis.
"Glioblastoma can be thought of as a wound that never stops healing," said Dr. Dirks.
"We are excited to see what tells us about how cancer originates and grows, and it opens up entirely new ideas for treatment by focusing on the injury and inflammatory response."
In their study, Dr. Dirk and colleagues use single-cell RNA sequencing and machine learning technologies to determine the molecular composition of glioblastoma stem cells responsible for tumor initiation and post-treatment recurrence.
The team found new subpopulations of glioblastoma stem cells that carry the molecular characteristics of inflammation and are associated with other cancer stem cells in patients' tumors.
These results, according to Dr. Dirks, suggest that some glioblastomas begin to form when the normal tissue healing process – designed to create new cells to replace those lost from injury – derails through mutations.
This could take many years before a patient becomes symptomatic.
Once a mutated cell is involved in wound healing, it doesn't stop multiplying – if all normal controls are broken – and spur tumor growth, the team said.
"The goal is to identify a drug that will kill the glioblastoma stem cells," said paper author and molecular geneticist Gary Bader of the University of Toronto.
"But we first had to understand the molecular nature of these cells in order to be able to target them more effectively."
The researchers collected GSCs from the tumors of 26 patients – and expanded them in the laboratory to obtain sufficient numbers of the rare cells for analysis.
In total, they analyzed almost 70,000 cells using single-cell RNA sequencing – a technique that detects which genes are switched on in individual cells.
Canadian researchers analyzed cells from tumors from 26 patients with a common but aggressive form of brain tumor known as glioblastoma. Glioblastoma cells shown
The team found evidence of “extensive disease heterogeneity” – which means that each tumor contained several subpopulations of molecularly different cancer stem cells.
This makeup increases the likelihood of cancer recurrence as existing therapies are unable to eradicate all of the various "subclones".
In addition, each tumor had one or both of two molecular states – referred to as the "developmental response" and the "injury response".
The developmental state is a hallmark of glioblastoma stem cells – and is similar to that of the rapidly dividing stem cells in the growing brain before birth, the researchers explained.
However, the second condition is surprising, the researchers said.
They called it "Injury Response" because it showed upregulation of immune pathways and inflammation markers – such as interferon and TNFalpha – that indicate wound healing processes.
Meanwhile, experiments found that the two conditions are prone to different types of gene knockouts, and revealed a number of therapeutic targets related to inflammation that had not previously been considered for glioblastoma.
Ultimately, the relative coming of the two conditions was found to be patient specific, meaning that each tumor was biased toward either the developmental or injury response end of the gradient.
After completing their first study, the researchers are now trying to target these biases to tailored therapies.
"We are now looking for drugs that are effective at different points on this gradient," said paper author and cancer genomicist Trevor Pugh of the Princess Margaret Cancer Center in Toronto.
"There is a real opportunity here for precision medicine – to prepare tumors in patients at the single cell level and to develop a drug cocktail that can remove more than one cancer stem cell subclone at the same time."
The full results of the study were published in the journal Nature Cancer.
WHAT IS A GLIOBLASTOME AND HOW FATAL IS IT? JOHN MCCAIN'S AGGRESSIVE BRAIN TUMOR
Senator John McCain was diagnosed with glioblastoma in July 2017
Glioblastoma is considered to be the most aggressive tumor that can form in the brain. Senator John McCain was diagnosed with one in July 2017.
According to figures, patients have a 10 percent chance of survival five years after their diagnosis. The average lifespan is between 14 and 16 months.
Three adults in every 100,000 will have glioblastoma, says the American Association of Neurological Surgeons (AANS).
It is most common in men between the ages of 50 and 60, and there is no association between developing glioblastoma and a history of other cancers.
WHAT IS THE TUMOR?
The tumor is made up of a mass of cells that grow rapidly in the brain, and in most cases, patients have no family history of the disease.
It won't spread to other organs, but once diagnosed it's nearly impossible to target, surgeons claim.
Unlike other types of brain cancer that are more specifically localized, glioblastoma can occur in any part of the brain.
WHAT TREATMENT IS AVAILABLE?
Because the tumor is likely to be deep in the brain by the time it is diagnosed, the cancerous tissue is incredibly difficult to remove.
The surgeon will only remove the tumor or part of the tumor if he does not damage the surrounding brain tissue.
Dr. Babcar Cisse, neurosurgeon at the Weill Cornell Brain and Spine Center, told Daily Mail Online in July 2017, “When glioblastoma is diagnosed, microfibers can spread to the rest of the brain that an MRI would not detect.
"Even if the main tumor is removed and the patient receives radiation and chemotherapy, they'll come back."
EVALUATION OF A GLIOBLASTOMA
Brain tumors are ranked between one and four based on how fast they grow and how aggressive they are.
Malignant tumors get either high grade three or four, while benign tumors get lower grade one or two.
Glioblastoma is often referred to as grade 4 astrocytoma – another type of brain tumor, the AANS says.
Patients usually complain of symptoms such as impaired vision, impaired memory, dizziness, and headache.
Symptoms are somewhat non-specific and vary from person to person and may not persist.
It is therefore impossible to diagnose the disease based on symptoms alone.
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