3 minute read
canadian researchers may have pinpointed the primary cause of glioblastoma, potentially unlocking new therapies for the highly aggressive form of brain cancer.
the study suggests the devastating disease — which claimed the lives of canadian musician gord downie and u.s. politician john mccain — arises as a result of cell mutations that occur during the healing process following a stroke or other brain injury. the research, published this week in nature cancer , offers hope for patients who currently live an average of just 15 months after receiving their diagnosis.
“ glioblastoma can be thought of as a wound that never stops healing, ” said peter dirks, head of neurosurgery and a senior scientist at the hospital for sick children (sickkids) in toronto , in a university of toronto press release. “ our data suggest that the right mutational change in particular cells in the brain could be modified by injury to give rise to a tumour.
“ we are excited about what this tells us about how cancer originates and grows and it opens up entirely new ideas about treatment by focusing on the injury and inflammation response. ”
glioblastomas occur in 4 out of every 100,000 people in canada, according to the brain tumour foundation , and can arise at any time , although they usually develop between the ages of 45 and 75. the disease is the most aggressive malignant primary brain tumour and can carry with it a host of symptoms — including headaches, weakness in the extremities, nausea and vomiting and even personality deficits — depending on the location of the tumours.
advertisement
treat ing glioblastoma is extremely difficult due to the ability of tumours to imbed themselves deep in the brain and resist conventional therapy. it is further complicated by the delicate nature of the surrounding tissue and the brain ’ s limited ability to heal itself. g lioblastoma is almost impossible to eradicate once it takes root without permanently altering the host.
“ the tumours still have a habit of coming back, even if you thought you got it all, because there ’ s still a few cells left that have been crawling deeper into the brain that have the capacity to multiply and cause the tumours to regrow ,” dirks told cbc . “we have the challenge that parts of your brain are essential for function, even the essence of who we are and how we communicate and how we laugh at jokes. we don’t want to remove or harm those areas that are essential for us to function and make us the people who we are.”
to arrive at their ground-breaking results, researchers mapped out the molecular makeup of glioblastoma stem cells (gscs) — the part of the disease that causes tumours in the brain of patients — using single cell rna sequencing and other advanced technologies . they then collected the gscs from the tumours of 26 patients and analyzed them using the same technique. this revealed the tumours were highly diverse across patients and that each tumour exist ed on a gradient between two states, which they dubbed “developmental” and “injury response.”
advertisement
the injury response state came as a surprise to researchers because the gscs at work here exhibited an upregulation of immune pathways and other markers that are indicative of a healing wound. this is evidence, dirk said, that some glioblastomas have their origins in mutations that occur during the tissue healing process that may not become evident until years later.
because gscs can exist on different points on the gradient between two states, any potential treatment would need to be patient specific, said trevor pugh, s enior s cientist at the princess margaret cancer centre in toronto. “ there is a real opportunity here for precision medicine — to dissect patients ’ tumours at the single cell level and design a drug cocktail that can take out more than one cancer stem cell subclone at the same time .”
dave yasvinski is a writer with healthing.ca
