Health
Can scientists learn how to prevent brain tumors?
David Ashley, M.D., Rory David Deutsch Distinguished Professor of Neuro-Oncology and director of Duke’s Preston Robert Tisch Brain Tumor Center, describes his choice to focus his career on brain tumors as “overcoming this terrifying problem.” I call it the impulse for
“When I was 23, my father passed away from a very nasty cancer,” Ashley said. At the time, he was an intern who had just started his residency. He said, “He had a dream of becoming an infectious disease doctor, but in the wake of his death there was a catalyst for cancer.” And obviously, brain tumors were the worst type of cancer. ”
Today, Ashley and his research team are one step closer to defeating brain tumors before they start.
Some background: Ashley’s lab has been studying a protein called STING (stimulator of the interferon gene). This protein normally detects DNA damage and signals the immune system to repair it. They found that this pathway was turned off in brain tumors.
“Thus, brain tumors form in an environment that lacks immunodetection capabilities. If we can restore these pathways in brain tumors, it could be a therapeutic cornerstone,” Ashley said. The team tried it in a human brain tumor cell line and found that drugs used to treat myelodysplastic syndrome and acute myeloid leukemia can reverse this pathway. was published in Cancer Cell.
This DNA damage detection pathway is turned off not only in adults with brain tumors, but also during normal fetal development. Ashley’s team therefore suspected that brain tumors may utilize other mechanisms meant to work only before the baby is born.
As a result, we are collaborating with a Norwegian group, experts in whole-genome sequencing and other new genomic techniques and computational methods, to search for the “cell of origin” of brain tumors. “Certain genes are switched on and off as cells in the brain mature and make connections,” he says. “But there are certain types of cells that are actually meant to disappear. It’s not even meant to exist in the human adult brain. And if you look at those cells, you’re very likely to be in glioblastoma.” very similar to.”
By studying human fetal atlas and brain tumor tissue, the research team found evidence that this cell is the ‘seed cell’ that initiates glioblastoma. Glioblastoma is a fast-growing, aggressive, and most common primary brain tumor.
“This means that the earliest stages of glioblastoma formation occur when the patient is still a developing fetus,” Ashley said.
If researchers can confirm these findings and develop a non-invasive test, such as a blood test, to detect these cells in babies, it could be a clue that those babies are at risk for brain tumors later in life. increase.
“I think what’s important is that the fetal cells remain in the adult,” Ashley said. “And if we can detect these fetal cells in at-risk people, we may be able to prevent brain tumors by developing drugs that stop the original cells from progressing.”
To build a foundation for that vision, the researchers will next detect these cells of origin in the brains of deceased brain tumor patients, and look for them in the brains of those who did not have brain tumors and who donated their brains for the study. The brain tissue is available through a partnership with the Department of Defense, Ashley said.
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