New Drug, CT-179, Holds Promise for Treating Medulloblastoma

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New Drug, CT-179, Holds Promise for Treating Medulloblastoma


New Drug, CT-179, Holds Promise for Treating Medulloblastoma
Credit: humonia / iStock / Getty Images Plus

Researchers from Emory University and QIMR Berghofer Medical Research Institute in Queensland, Australia, have demonstrated that a potential new targeted therapy for treating medulloblastoma (MB) was shown to be effective killing tumor cells in mouse models. The new drug, called CT-179, can infiltrate and kill tumor cells by targeting a subset of cancer stem cells that are resistant to standard treatments, the researchers reported in Nature Communications.

“Current treatments, including radiation and chemotherapy, often eliminate most of the tumor, but sometimes fail to eliminate cancer stem cells,” said Timothy Gershon, MD, PhD, one of the lead researchers of the study and a professor of neuro-oncology at Emory University School of Medicine. “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.”

CT-179 targets a protein called OLIG2, a known marker for stem cells involved in the initiation and recurrence of brain cancers. This new drug was shown to be particularly effective in treating the Sonic Hedgehog (SHH) subtype of medulloblastoma. This subtype is one of the most challenging of the four medulloblastoma subtypes to treat as it is often resistant to standard therapies and has a high rate of recurrence. SHH-driven medulloblastoma accounts for about 25% of all MB cases, with the highest incidence seen in infants and young children.

The childhood brain cancer medulloblastoma is typically treated with radiation and chemotherapy. While these approaches can prolong survival, they often cause long-term cognitive and physical side effects, especially when applied to infants with this form of cancer. The potential of CT-179 is its ability to provide a more targeted approach, disrupting the specific stem cells that drive tumor regrowth, while leaving other healthy cells unharmed and reducing side effects

The study used a variety of preclinical models to evaluate the effectiveness of CT-179. Researchers conducted experiments on human MB cell lines, patient-derived tumor organoids, and genetically modified mice with medulloblastoma. The results showed that CT-179 was effective at inhibiting OLIG2, leading to the destruction of tumor cells and preventing their ability to regenerate.

CT-179 was also tested in combination with radiation therapy, with encouraging results. “Our study demonstrated that the drug CT-179, used in combination with standard radiation therapy, can cross the blood-brain barrier and penetrate the tumor. It prolonged survival in a range of preclinical medulloblastoma models, delayed recurrence of the disease, and increased the effectiveness of radiotherapy,” said senior author Bryan Day, PhD, group leader at QIMR Berghofer Medical Research Institute.

The potential for CT-179 extends beyond medulloblastoma. The drug has shown effectiveness against other brain tumors such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), which also present major challenges in pediatric cancer treatment.

“This global research could potentially lead to new combination therapies that improve outcomes for these young patients,” said Day. “What gets us out of bed every day is trying to solve the puzzle of brain cancer.”

While the results are promising, researchers said that further studies will be necessary to confirm the drug’s safety and efficacy in humans. One key concern is the potential impact of CT-179 on normal brain function, particularly its effects on myelination. However, preliminary data suggest that CT-179 does not affect myelinating cells, which is crucial for ensuring that the drug does not harm normal brain tissue.

The researchers plan to launch a clinical trial to determining the optimal combination therapies that could enhance the effects of CT-179, including pairing it with other targeted drugs like palbociclib to prevent resistance.



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