Scientists Identify Protein That Could Make Glioblastoma More Vulnerable to Treatment

Scientists at the Ohio State University Comprehensive Cancer Center have identified a potential therapeutic target whose inhibition could make glioblastoma cells more sensitive to treatment. The target is the protein SET, which is involved in a mechanism that allows tumor cells to survive and resist therapy.

The findings were published in the journal Cancer Letters.

Glioblastoma remains one of the most aggressive and difficult-to-treat forms of cancer. Tumors often develop resistance to radiation and chemotherapy, so researchers are looking for ways not to replace existing treatments but to make them more effective.

The scientists focused on the enzyme PP2A, which regulates signaling pathways involved in the growth and survival of cancer cells, as well as their ability to recover from treatment-related damage.

The researchers found that glioblastoma cells can suppress PP2A activity through three proteins — ANP32A, CIP2A, and SET. Blocking these proteins in laboratory and animal models reduced cancer cell survival and increased their sensitivity to radiation therapy.

SET emerged as the most promising target: suppressing the protein prevented tumor formation in preclinical models.

“Glioblastoma is difficult to treat because it can adapt and survive. Our findings suggest that restoring PP2A activity may deprive glioblastoma cells of their ability to resist treatment,” said Arnab Chakravarti, chair of the Department of Radiation Oncology at the Ohio State University Comprehensive Cancer Center.

The researchers also tested an FDA-approved antipsychotic drug that can increase PP2A activity. According to the scientists, the results support further investigation of drugs that target this mechanism.

However, the findings are still preliminary and have not been tested in patients. Researchers still need to determine whether SET or other proteins that suppress PP2A can be safely targeted and whether doing so can actually improve the effectiveness of standard glioblastoma treatment.

The researchers specifically emphasized that the drug tested in the study is not currently intended to treat glioblastoma and should not be used for this purpose outside of clinical trials.