Making glioblastoma more vulnerable to treatment

In the tough war against glioblastoma, scientists are taking a cue from viruses on how to make the aggressive cancer more vulnerable to treatment.

Their target is SAMHD1, a protein which can protect us from viral infections by destroying an essential building block of DNA that viruses and cancer need to replicate.

But they’ve found SAMHD1 also has the seemingly contradictory skill of helping repair double-strand breaks in the DNA that if unrepaired can be lethal to any cell, including a cancer cell, and if mended incorrectly can result in genetic mutations that produce cancer.

“When the DNA breaks, that is what actually interrupts the DNA replication and also the synthesis of proteins, so a double-strand break is lethal for cells,” says Waaqo Daddacha, PhD, cancer biologist in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia.

Cancer cells, which are reproducing much more rapidly than most normal cells, are replicating even faster, so are impacted even more by these DNA breaks, which is why fundamental therapies like radiation and some chemotherapy drugs used to treat cancers make these lethal breaks.

However, the aggressive brain cancer quickly becomes treatment-resistant and the average survival remains at about 15 months, Daddacha says.

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