Researchers Develop New Treatment Method for Common Brain Tumor in Children

Researchers at McMaster University have recently found a way to make medulloblastoma, the most common type of pediatric brain tumor, respond better to treatment.

Branavan Manoranjan, M.D., Ph.D., first author of the published paper in the journal Nature Communications, titled, "Wnt activation as a therapeutic strategy in medulloblastoma," mentioned that the Wnt pathway could function as a tumor suppressor. 

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Medulloblastoma is an aggressive malignant tumor of the cerebellum, the part of the brain that controls balance, coordination, and other complex functions. This type of tumor can affect any age group, but most commonly affects children. Although it is still considered a rare disease, it is the most common type of cancerous brain tumor among children.

Medulloblastoma is a type of embryonal tumor, the kind that starts in the fetal or embryonic cells in the brain. It then spreads through the cerebrospinal fluid (CSF) but rarely spreading to the other areas of the body.

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Common signs and symptoms include headaches, nausea, vomiting, tiredness, dizziness, double vision, poor coordination, unsteady walk, and other concerns. This may be due to the tumor itself or the cause of built-up pressure in the brain.

Medulloblastoma has been recently categorized into four molecular subtypes. Group 1 tumors rarely metastasize, and are rarely lethal. Groups 2, 3, and 4 are more aggressive compared to Group 1. They spread quickly, and are seen to be deadly in 20 to 30 percent of patients despite full treatment.

Studies done by the team has found all different subtypes to contain a fraction of Wnt active cells, which is promising when it comes to treatment responsiveness. The Wnt signaling pathway is a conserved pathway responsible for the regulation of crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning, and organogenesis during embryonic development.   

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Group 1 MB, also called the Wnt subtype, has the most favorable prognosis with more than a 95 percent five-year survivorship. Non-Wnt MBs, on the other hand, are characterized by metastatic disease, increased rates of recurrence, and intermediate-poor overall survivorship.

Based on these results, Wnt MBs represent the only subgroup in which it can have a remarkable response to therapy. The results are also not indicative of a poor prognosis. 

Branavan and his team's newly conducted research in the lab of senior author, Sheila Singh, Ph.D., a professor in surgery and biochemistry at McMaster University, identified a small molecule that turned on the Wnt Pathway. This was the result of mice with non-Wnt subtype medulloblastoma tumors that were tested were found to display reduced tumor growth and improved survival.

They do acknowledge that before considering Wnt as a treatment for medulloblastoma, it is vital to identify first the mechanisms in which Wnt signaling can target genes that impede cancer growth. 

Singh concluded that a drug currently in use for the treatment of other conditions had been found to selectively and specifically activate Wnt signaling.

Molecular oncology trials are continuously developing, and approaches to cancer will still be altered, such as reactivating anti-oncogenic programs that have been previously silenced in a tissue-specific manner. In the end, Singh mentioned that Wnt activation presents an innovation in the therapeutic response against treatment-resistant medulloblastoma.

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