Rather than replacing current treatments, the strategy is designed to help them work better. In preclinical experiments, suppressing SET prevented tumors from developing.

A Potential Weakness in Glioblastoma

Among the proteins examined, SET stood out because blocking it had such a strong effect on tumor formation. The researchers also found that interfering with related proteins increased the sensitivity of glioblastoma cells to radiation.

Together, the findings point to a biological pathway that may eventually be targeted with drugs to weaken the cancer's defenses.

The OSUCCC - James team focused on PP2A, an enzyme involved in regulating signals that cancer cells use to grow, survive, and recover from treatment-related damage. Glioblastoma cells appear to interfere with PP2A using three proteins called ANP32A, CIP2A and SET. When the researchers blocked those proteins in laboratory and animal models, fewer cancer cells survived, and the remaining cells became more vulnerable to radiation.

"Glioblastoma is hard to treat because it can adapt and survive," said Arnab Chakravarti, MD, chair of radiation oncology at the OSUCCC - James. "Our findings suggest that restoring PP2A activity may make glioblastoma cells less able to survive treatment. That gives us a clear path to test whether this approach can make radiation and chemotherapy more effective for patients with GBM."

Testing Ways to Restore PP2A Activity

The results remain preliminary and have not yet been evaluated in patients. Researchers are now investigating whether SET or other proteins that suppress PP2A can be targeted safely and whether doing so improves the effectiveness of standard glioblastoma therapies.

The team also examined an FDA-approved antipsychotic drug that is capable of increasing PP2A activity. According to the researchers, the results provide additional reason to study medications that influence this pathway.

However, the drug is not ready to be used as a glioblastoma treatment and should not be taken for this purpose outside a clinical trial.

"This is an important first step," said Chakravarti. "By understanding how SET and related PP2A blockers help GBM survive treatment, we can test ways to block that protection and make current therapies more effective."

A First Step Toward New Treatment Strategies

The study was published in the May 2026 issue of Cancer Letters, and was supported by grants from the National Institutes of Health, National Cancer Institute and The Ohio State University Comprehensive Cancer Center.