Title:Targeting brain cancer biomarkers

Biomarkers that could be targets for novel drugs to treat glioblastoma brain tumors have been identified by investigators at Georgetown Lombardi Comprehensive Cancer Center.

Currently, the drug most often used to treat glioblastoma, temozolomide, is uniquely able to cross the blood/brain barrier to attack the tumor, but resistance develops rapidly, and many patients do not survive for more than a year after diagnosis. This new finding provides early evidence that there may be a benefit in targeting specific alterations in cancer cells with newer agents once a patient’s tumor becomes resistant to temozolomide.

“As a field, we have struggled to deal with the short-term effectiveness of temozolomide, as many of the drugs used successfully in other cancers are disappointing when they are subsequently tested in glioblastoma clinical trials. One way to deal with this problem is to learn enough about how we can target features that help drug-resistant glioblastoma survive,” says Rebecca B. Riggins, Ph.D., associate professor and associate director of education and training at Georgetown Lombardi and co-corresponding author of the study that appeared in the June 2022 issue of Science Advances.

“We focused on the details of how temozolomide damages DNA to help radiation treatments work better. Our team found that temozolomide resistant glioblastoma relies on a protein called CLK2, and that inhibiting the activity of CLK2 could cause widespread confusion, leading to cancer cell death.”

The investigators are now undertaking studies in small animal models, where they will test to see if the novel CLK2 inhibitor can efficiently enter the brain and shrink temozolomide-resistant glioblastoma.