Glioblastoma: Could Targeting SET Improve Radiation

What did researchers discover about SET and glioblastoma?

Researchers at The Ohio State University Comprehensive Cancer Center investigated proteins that help glioblastoma cells maintain growth and resist treatment. Their study appeared in the May issue of Cancer Letters and was highlighted by the university in August. SET stood out because suppressing it prevented tumors from developing in the models studied. [Ohio State research announcement](https://www.eurekalert.org/news-releases/1139160)

The distinction between preventing experimental tumor formation and treating an established human cancer is crucial. These results identify a biological dependency that researchers may be able to exploit. They do not demonstrate that a medicine targeting SET can eliminate an existing glioblastoma, prevent recurrence after surgery, or extend a patient's life. Those clinical questions remain unanswered.

How could restoring PP2A activity weaken treatment resistance?

The study examined protein phosphatase 2A, or PP2A, an enzyme that regulates cellular signaling. Researchers found that glioblastoma specimens overexpressed three proteins that inhibit it: ANP32A, CIP2A and SET. Suppressing these inhibitors restored PP2A activity and disrupted signaling associated with cancer growth. This suggests a potential way to interfere with several survival mechanisms within the tumor.

Using CRISPR-Cas9 gene editing in experimental cells, the team also linked these inhibitors to radiation resistance. Their removal affected ATM and ATR, proteins involved in responding to DNA damage, and increased radiation sensitivity. The implication is that weakening the tumor's damage response might improve treatment effectiveness, although this remains an experimental strategy. The researchers were not administering gene editing to patients. [Original Cancer Letters study](https://pmc.ncbi.nlm.nih.gov/articles/PMC13250921/)

What does this research mean for glioblastoma treatment today?

The National Cancer Institute describes surgery followed by radiation and temozolomide chemotherapy as standard treatment for many patients with newly diagnosed glioblastoma. Surgical decisions must balance tumor removal with preservation of neurological function. Treatment selection also depends on the patient's health and tumor characteristics. The SET findings provide a research direction without establishing a replacement for these treatments. [NCI treatment guidance](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq)

Ohio State reports that the team also investigated an approved antipsychotic capable of increasing PP2A activity. Approval for a psychiatric condition does not establish effectiveness against glioblastoma, and the researchers advise against using it for this purpose outside a clinical trial. Future studies must determine whether this pathway can be targeted safely and whether doing so improves outcomes when combined with standard care. [Ohio State research announcement](https://www.eurekalert.org/news-releases/1139160)