Ohio State University researchers have identified a molecular pathway that may help glioblastoma resist radiation and sustain tumor growth, according to findings newly highlighted on Sunday. The team found that three proteins called SET, ANP32A and CIP2A suppress protein phosphatase 2A, or PP2A, an enzyme that normally restrains several cancer-promoting signals. The results are preclinical and do not establish a treatment for patients.
Glioblastoma is the most common primary brain cancer in adults and is exceptionally aggressive. Surgery, radiation and chemotherapy remain standard care, yet tumors frequently return because their cells adapt to treatment and repair damage. The study, published in the May 2026 issue of the peer-reviewed journal Cancer Letters, asked how glioblastoma keeps growth-related kinase networks active even though the tumor-suppressing PP2A enzyme remains genetically intact.
Researchers analyzed public RNA and protein data from normal brain and glioblastoma tissue, examined patient samples and used established and patient-derived cancer cell lines. They found elevated levels of SET, ANP32A and CIP2A in tumors. Using CRISPR-Cas9 gene editing, the scientists removed each inhibitor and observed increased signs of PP2A activity, indicating that the proteins help shield malignant signaling from the enzyme.
In mouse experiments, cells lacking SET did not form detectable brain tumors during the 100-day observation period, while removal of ANP32A or CIP2A produced more modest extensions in survival. The team also found that silencing the inhibitors made glioblastoma cells more sensitive to radiation by impairing ATM and ATR pathways involved in repairing DNA damage and controlling cell-cycle checkpoints. These experiments used laboratory models, not human participants.
The findings suggest that restoring PP2A activity by targeting its endogenous inhibitors could attack several tumor-supporting pathways at once and potentially strengthen radiation therapy. The researchers particularly identified SET as important for tumor formation and described CIP2A as a possible route for modifying the DNA-damage response. However, PP2A acts on many cellular targets, so safety, selectivity and the effects on normal tissue require careful testing.
The authors said the work provides a first step toward evaluating medicines that influence this pathway. No drug tested in the study is approved as a glioblastoma therapy, and the researchers cautioned against using such compounds outside clinical trials. Further studies must confirm the results in additional models, determine which target offers the best therapeutic window and establish safety before any human trial can assess whether the approach improves outcomes.
Comments