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Potential Target Inhibits Growth of Glioblastoma

Findings may lead to increased survival in patients with glioblastoma.

A potential new target shows promise in the treatment of glioblastoma.

By targeting a protein that drives the growth of brain tumors, the investigators were able to inhibit the growth of glioblastoma, according to a study published in Cell Reports.

“These findings change our fundamental understanding of the molecular basis of glioblastoma, and how to treat it,” said co-senior author Dr Robert Bachoo. “We may have identified a set of critical genes we can target with drugs that are shared across nearly all glioblastomas.”

Current treatment options for glioblastoma included surgery followed by chemotherapy and radiation. However, due to the aggressive nature of the cancer, the regimen only improves median survival by 4 to 6 months, and is followed by tumor recurrence. If the tumor recurs, there is not successful treatments available. The 5-year survival rate is approximately 5%.

In the new study, investigators used genetics to help guide potential treatment strategies.

“Our work shows that the gene mutations which the pharmaceutical industry and clinicians have been focusing on are essential only for starting tumor growth,” Dr Bachoo said. “Once the tumor has advanced to the stage where patients seek treatment, these mutations are no longer required for continued tumor growth; they are in effect redundant.”

Previously, scientists believed receptor tyrosine kinase proteins were drivers of glioblastoma. However, drugs that inhibit these proteins have been ineffective.

“We learned that, instead, it is neurodevelopmental transcription factors (master proteins that regulate the activity of hundreds of genes during normal brain development), which are reactivated to drive the growth of glioblastoma,” said co-senior author Dr Ralf Kittler. “We can inhibit these transcription factors and prevent further tumor growth with the chemotherapy drug mithramycin, a drug that has not been in clinical use for years due to its side effects.

“Our discovery has the potential for the development of a new therapy that may increase survival time for glioblastoma patients.”

The authors noted that repurposing mithramycin and pairing it with treatments with more safety and efficacy to treat glioblastoma could take years.

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