Brain cancer is the second leading cause of death in children in developed countries. Despite advancements in medical treatments, many survivors face long-term developmental and quality-of-life issues. However, a recent discovery from Emory University and QIMR Berghofer Medical Research Institute in Brisbane may offer hope.

Novel Drug Shows Promising Results in Mice Models

Researchers have identified a potential new targeted therapy for childhood brain cancer, CT-179, which effectively infiltrates and kills tumor cells in preclinical models tested in mice. This drug has been found to specifically target a specific subset of tumor cells responsible for recurrence and therapy resistance in pediatric brain cancer.

The findings, published in Nature Communications, could lead to more effective, less toxic treatments, significantly improving survival rates and the quality of life for young patients. The lead researchers believe the findings could be transformative not only for medulloblastoma, the most common childhood brain cancer, but also for other brain cancers such as glioblastoma and diffuse intrinsic pontine glioma.

The Role of Cancer Stem Cells and CT-179

Timothy Gershon, an Emory University Professor and pediatric neurologist at Children’s Healthcare of Atlanta, highlighted the importance of targeting cancer stem cells in the treatment of brain tumors. Common treatments, including radiation and chemotherapy, effectively eliminate tumor cells but often leave behind cancer stem cells, which can regrow tumors and cause fatal recurrence. Dr. Gershon explained that CT-179 disrupts these stem cells.

“Current treatments, including radiation and chemotherapy, often eliminate most of the tumor, but sometimes fail to eliminate cancer stem cells,” Dr. Gershon stated. “These cancer stem cells can regrow the tumor after treatment, causing fatal recurrence. We show that CT-179 treatment specifically disrupts cancer stem cells. Combining CT-179 with treatments such as radiation therapy treats the whole tumor more effectively, including both stem cells and tumor cells that are not stem cells.”

Collaborative Efforts and the Potential Impact

Emory University researchers collaborated with Curtana Pharmaceuticals, a U.S. drug company, to develop the experimental small molecule drug CT-179. The drug effectively targets the OLIG2 protein, a stem cell marker crucial in the initiation and recurrence of brain cancers.

Bryan Day, leader of QIMR Berghofer’s Sid Faithfull Brain Cancer Laboratory and co-director of the Children’s Brain Cancer Centre in Australia, emphasized the importance of this discovery and its potential impact. “Children with brain cancer urgently need more effective and less toxic treatments,” he said. “Our study demonstrated that the drug CT-179, used in combination with standard radiation therapy, can cross the blood-brain barrier and penetrate tumors. It prolonged survival in a range of preclinical medulloblastoma models, delayed recurrence of the disease, and increased the effectiveness of radiotherapy.”

Complementary Research and the Future of Cancer Treatment

The findings from the QIMR Berghofer and Emory University studies complement the results of another study published in Nature Communications led by Professor Peter Dirks of the University of Toronto and neurosurgeon-in-chief at the Hospital for Sick Children in Canada.

Through advanced tools like CRISPR gene editing, single-cell RNA sequencing, and collaborative drug testing, the study identified the OLIG2 protein as a key regulator of tumor growth transitions in medulloblastomas, a common childhood brain tumor.

“Our study demonstrated that the OLIG2 protein is a critical driver of the complex early stages of medulloblastoma tumor formation, making it a highly promising treatment target,” Dr. Dirks said. “We showed that inhibiting the OLIG2 protein with the CT-179 drug prevented cancer stem cells from changing to a proliferative state, effectively blocking the growth and recurrence of tumors. This could have potentially profound implications for treatment in the future.”

Conclusion: A Step Forward in Child Cancer Research

The discovery of CT-179 and its ability to target cancer stem cells represents a significant step forward in the treatment of childhood brain cancer. With these findings, researchers come closer to providing more effective and less toxic treatment options for young patients, while improving their chances of survival and enhancing their quality of life.