Glioblastoma, one of the deadliest cancers known to humanity, has been laughing in the face of radiation and chemotherapy for decades. But researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute have found a chink in its armor: a protein called SET. Blocking SET, they say, could make glioblastoma cells more susceptible to existing treatments, which is a bit like discovering that the invincible fortress has a door that was just painted to look like a wall.

The strategy isn't to replace current therapies but to give them a boost. In preclinical experiments, suppressing SET prevented tumors from forming. SET stood out among the proteins examined because blocking it had such a dramatic 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 could be targeted with drugs to weaken the cancer's defenses. The team focused on PP2A, an enzyme that regulates signals cancer cells use to grow, survive, and recover from treatment damage. Glioblastoma cells appear to interfere with PP2A using three proteins: ANP32A, CIP2A, and SET. When these proteins were blocked in lab and animal models, fewer cancer cells survived, and the rest 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, in a statement that will surprise no one who has ever read about glioblastoma. "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."

The results are preliminary and haven't been tested in humans yet. Researchers are now investigating whether SET or other PP2A-suppressing proteins can be targeted safely, and whether doing so improves standard glioblastoma therapies. They also examined an FDA-approved antipsychotic drug that can increase PP2A activity, providing additional reason to study medications that influence this pathway. But hold your horses - this drug is not ready for prime time as a glioblastoma treatment and should not be taken for that 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."

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. Materials were provided by Ohio State University Wexner Medical Center. Content may be edited for style and length - because science news, like tumors, sometimes needs a little trimming.