Scientists find a weak spot in one of the deadliest brain cancers
Researchers may have found a new way to weaken glioblastoma’s defenses against treatment. Blocking a protein called SET prevented tumors from forming in preclinical models, while targeting related proteins made cancer cells more vulnerable to radiation. The strategy works by restoring activity of PP2A, an enzyme that glioblastoma cells appear to suppress. Human testing will be needed to determine…
Glioblastoma, one of the deadliest forms of cancer, has shown limited improvement in treatment options due to its ability to resist radiation and chemotherapy. Researchers from The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute have identified a protein, SET, which could potentially enhance the effectiveness of existing therapies.
In preclinical experiments, suppressing SET hindered tumor development. Blocking SET in combination with other related proteins increased glioblastoma cells' sensitivity to radiation. The study focused on PP2A, an enzyme regulating signals that cancer cells utilize for growth, survival, and recovery after treatment. When blocking specific proteins (ANP32A, CIP2A, and SET) in lab models and animal experiments, fewer cancer cells survived, and the remaining cells became more vulnerable to radiation.
Lead researcher, Dr. Arnab Chakravarti, stated that restoring PP2A activity may make glioblastoma cells less capable of surviving treatment, offering a clear path to test if this approach can improve the effectiveness of radiation and chemotherapy for GBM patients. The findings are preliminary and have yet to be evaluated in patients.
Researchers are currently investigating the safety of targeting SET or other proteins that suppress PP2A and their potential to enhance standard glioblastoma therapies. An FDA-approved antipsychotic drug, which can increase PP2A activity, is also being studied, although it is not yet ready for glioblastoma treatment outside of clinical trials.
This research, published in the May 2026 issue of Cancer Letters, represents a significant first step in understanding how SET and related PP2A blockers help glioblastoma cells survive treatment and could lead to ways to block this protection, making current therapies more effective.
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