Research indicates that a promising new targeted therapy for pediatric brain cancer has proven effective in penetrating and eliminating tumor cells during preclinical testing on mice. The innovative medication, CT-179, targets a specific group of tumor cells that contribute to recurrence and resistance to treatment in children with brain cancer. This breakthrough may pave the way for more effective and less harmful treatments, ultimately enhancing survival rates and life quality for young patients.
Brain cancer ranks as the second leading cause of mortality among children in developed nations. For those who do survive, conventional treatments can lead to long-lasting effects on their development and overall well-being, especially in very young children and infants.
Research conducted at Emory University and the QIMR Berghofer Medical Research Institute in Queensland, Australia, has unveiled that a potential new targeted therapy for pediatric brain cancer can effectively infiltrate and destroy tumor cells in preclinical mouse models.
Published in Nature Communications, this novel drug, CT-179, was found to specifically target a subset of tumor cells that are responsible for the recurrence and resistance to therapy seen in pediatric brain cancers. These findings may result in the development of more effective treatments that are also less toxic, which would enhance the survival and quality of life for young patients.
The principal investigators believe these results could revolutionize the treatment of the most prevalent form of childhood brain cancer, medulloblastoma, and may also extend to other brain cancers like glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG).
Timothy Gershon, a professor at Emory University, pediatric neurologist at Children’s Healthcare of Atlanta, and director of the Children’s Center for Neurosciences Research, considers the study a major leap forward in our comprehension of the biological mechanisms that contribute to tumor growth and recurrence.
“While current treatments, like radiation and chemotherapy, often remove most of the tumor, they occasionally fail to target cancer stem cells,” Gershon explains. “These stem cells can regenerate the tumor post-treatment, leading to devastating recurrences. Our findings show that CT-179 specifically disrupts these cancer stem cells. When CT-179 is combined with therapies such as radiation treatment, it can address the entire tumor more effectively, managing both stem cells and non-stem tumor cells. Integrating CT-179 with existing treatments could enhance the effectiveness of brain tumor therapies.”
The research teams partnered with the U.S. pharmaceutical company Curtana Pharmaceuticals, which developed the experimental small-molecule drug CT-179. They discovered that the drug effectively targets the OLIG2 protein, a stem cell marker vital in the development and recurrence of brain cancers.
Professor Bryan Day, leading QIMR Berghofer’s Sid Faithfull Brain Cancer Laboratory and co-director of the Children’s Brain Cancer Centre in Australia, described the findings as groundbreaking, especially since they are based on independent studies.
“There is an urgent need for more effective and less toxic treatments for children with brain cancer,” Day states. “Our research showed that the drug CT-179, when used with standard radiation therapy, can penetrate the blood-brain barrier and reach the tumor. It extended survival in various preclinical models of medulloblastoma, postponed disease recurrence, and enhanced the efficacy of radiation therapy. Brain cancer presents an incredibly complex challenge. Our passion as researchers drives us to resolve this puzzle. This global research may open pathways to new combination therapies that can improve outcomes for these young patients,” Day explains.
The findings from QIMR Berghofer and Emory University complement results from another study published in Nature Communications led by Professor Peter Dirks from the University of Toronto, who is also chief neurosurgeon and a senior scientist at the Hospital for Sick Children (SickKids) in Canada.
This study focused on medulloblastomas, a common type of brain tumor in children. By employing advanced methods such as CRISPR gene editing, single-cell RNA sequencing, and collaborative drug testing, the researchers identified the OLIG2 protein as a crucial regulator of tumor growth transitions. This indicates a new therapeutic direction, shifting the focus from broad tumor treatments to specific strategies targeting tumor-initiating cells.
“Our research demonstrated that the OLIG2 protein plays a critical role in the complex early phases of medulloblastoma formation, positioning it as a highly promising target for treatment,” Dirks says. “We found that inhibiting the OLIG2 protein with CT-179 prevented cancer stem cells from entering a proliferative state, effectively halting tumor growth and recurrence. This could lead to significant advancements in treatment protocols in the future.”
