A research team has pinpointed a key factor that encourages tumor growth in a specific type of medulloblastoma and discovered a method to inhibit this process.
Researchers at The Hospital for Sick Children (SickKids) have uncovered a means to halt tumor growth before it begins for a subtype of medulloblastoma, which is the most prevalent form of malignant brain cancer in children.
Brain cancer poses distinct challenges for scientists; by the time symptoms arise, the tumors can become so intricate that the underlying processes driving their growth can be hard to determine. A research team led by Dr. Peter Dirks is striving to address this issue in sonic hedgehog (SHH) medulloblastoma.
A recent study published in Nature Communications reveals that a specific protein plays a role in awakening ‘sleeping’ stem cells, which contribute to the formation and resurgence of SHH medulloblastoma tumors. The study suggests that obstructing this protein and stopping the stem cells from activating could serve as a crucial therapeutic approach for this cancer, integrating advanced genomic techniques with practical trials in preclinical models.
“Our research introduces a new strategy to focus on cancer stem cells, creating possibilities for more effective treatments for aggressive brain tumors,” notes Dirks, who is a Senior Scientist in the Developmental, Stem Cell & Cancer Biology program and Chief of the Division of Neurosurgery.
Cancer interception in action
The researchers began their work by investigating the cellular changes that lead to the emergence of SHH medulloblastoma tumors. They discovered that early in tumor development, and after conventional treatments, a protein known as OLIG2 activates ‘sleeping’ stem cells, leading them to multiply and form a tumor.
“There’s a systematic way in which the cancer-initiating stem cells undergo changes that enable tumor formation. By targeting an early transition event, we can intercept the whole process – effectively halting the cancer at its initial stage,” explains Dr. Kinjal Desai, the first author and a postdoctoral researcher in Dirks’ lab.
During these transitions, the team identified a critical period when tumor advancement could be curtailed. By combining previously established treatments with a small molecule named CT-179, which inhibits the OLIG2 protein, the researchers were able to address the remaining stem cells after treatment and prevent their reactivation, thus avoiding tumor reoccurrence.
In similar trials involving early-stage SHH medulloblastoma, CT-179 successfully prevented tumor formation and significantly improved survival rates in preclinical models.
In conjunction with additional preclinical studies published simultaneously in Nature Communications by collaborators at Children’s Healthcare of Atlanta and QIMR Berghofer Medical Research Institute in Australia, these findings present a promising new treatment for SHH medulloblastoma, as well as other brain tumors such as diffuse intrinsic pontine glioma (DIPG).
This research complements recent findings from the Dirks Lab published in Nature that detail the initial phases of glioblastoma development. Although further investigations will work towards translating these results into clinical trials for patients, especially those being monitored for potential relapse, the Dirks lab, part of the Arthur and Sonia Labatt Brain Tumour Research Centre (BTRC), is enthusiastic about the diagnostic possibilities this finding may offer.
“At SickKids, we are already conducting genetic testing for every child with cancer to guide their diagnosis and treatment – our research moves beyond genetic analysis to focus on precision biology,” remarks Dirks. “I look forward to a future where this potential ‘magic bullet’ for early intervention can be paired with diagnostic tests to possibly prevent cancer from developing in the first place.”
This study has received funding from the Canadian Institutes of Health Research (CIHR), Ontario Institute for Cancer Research, Terry Fox Research Institute, Canadian Cancer Society, Cancer Research UK, Stand Up to Cancer, Jessica’s Footprint Foundation, Hopeful Minds Foundation, b.r.a.i.n.child, Meagan’s Walk, Garron Family Cancer Centre, the Bresler family, and SickKids Foundation.
