Blocking DNA-repairing protein could help beat glioblastoma

Suppressing the DNA-repairing protein, RAD51, boosted the efficacy of radiotherapy in treating glioblastoma, the most common malignant brain tumor in adults.

Glioblastoma can be difficult to treat because therapies typically only affect some tumor cells, while leaving others undisturbed. University of Leeds scientists may have found a workaround though: A protein in the brain that, when blocked, boosts the effectiveness of radiotherapy in destroying glioblastoma cells.

Glioblastoma is the most common malignant brain tumor in adults, and also the most aggressive. The Leeds team found that a particularly treatment-resistant subgroup of tumor cells, dubbed Glioblastoma Stem Cells (GSCs), contain a large amount of the protein, RAD51, which sabotages radiotherapy.

“Radiotherapy damages the DNA in the glioblastoma cells—but the RAD51 helps them to repair this damaged DNA, meaning they can repopulate the tumour,” said lead author Susan Short, a professor of clinical oncology and neuro-oncology at the University of Leeds, in a statement. “By targeting RAD51 with an inhibitor, we were able to make these GSCs more sensitive to the effects of radiotherapy, helping remove the tumour.”

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The researchers harvested tumor cells from glioblastoma patients and, using immunofluorescence microscopy, showed that these cells have higher levels of RAD51 than normal brain cells. They then treated the cells with an inhibitor and radiation.

“This promising study in cells and mice may have found a way to cut off the tumour’s fuel supply, which could one day help treatments target the disease more precisely and effectively,” said Dr. Justine Alford, senior science information officer at Cancer Research UK, which funded the study. “But more research is needed to find out if this strategy could be safe and effective in people.”

Scientists have long been seeking an effective treatment for glioblastoma, which generally has a poor prognosis. The American Brain Tumor Association pegged the two-year survival rate for adults at 30%.

In September, researchers from the University of Southampton found that suppressing a group of enzymes called ADAMs may slow the growth and spread of glioblastoma. In a similar approach, Ohio State scientists blocked the enzyme PRMT5, pushing tumor cells into senescence and reducing tumor growth. And in April, a group from Ottawa Hospital Research Institute discovered that inhibiting the oncostatin M receptor prevented tumor stem cells from forming new tumors in mouse brains.

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