Achilles Enzyme

A Possible New Target for Brain Cancer Drugs

Robert BaiocchiBalveen KaurA molecule in cells that shuts down the expression of genes might be a promising target for new drugs designed to treat the most frequent and lethal form of brain cancer, according to a new study by researchers at the OSUCCC – James.

The findings show that high levels of the enzyme PRMT5 are associated with aggressive growth of the brain cancer glioblastoma multiforme (GBM).

GBM is a highly invasive malignancy that strikes nearly 14,000 Americans annually. Average survival remains 15 months, even after surgery, chemotherapy and radiation. In this study, inhibiting PRMT5 significantly improved survival in an animal model of GBM. “Our findings suggest that PRMT5 is a possible prognostic factor and therapeutic target for glioblastoma, and they provide a rationale for developing agents that target PRMT5 in this deadly disease,” says co-corresponding author Robert A. Baiocchi, MD, PhD, a hematologist at the OSUCCC – James. Baiocchi is also collaborating on an Ohio State effort to develop a PMRT5 inhibitor.

“Our analyses also helped us identify PRMT5 as a master transcriptional repressor (gene silencer) in this disease, says co-corresponding author Balveen Kaur, PhD, professor and vice chair of research, Department of Neurological Surgery and of Radiation Oncology at Ohio State.

“We also learned that PRMT5 inhibition induced the death of glioblastoma cells whether the P53 gene was mutated or not. This has important treatment implications because loss of P53 is associated with a poor prognosis, so a PRMT5 inhibitor might be particularly important for these patients,” Kaur says.

Published in the journal Cancer Research.

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