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Study Identifies Possible New Target for Future Glioblastoma Drugs

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Key Points

  • High expression of PRMT5 in tumors was associated with more aggressive glioblastoma.
  • Patients with high PRMT5 tumor expression had shorter overall survival (108 days) compared to patients with medium expression (277 days) and low expression (726 days).
  • PRMT5 inhibition induced the death of glioblastoma cells whether the P53 gene was mutated or not, leading researchers to believe that PRMT5 inhibitor might be an important new target for future therapies.

A 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 Yan et al published in Cancer Research. The findings show that high levels of the enzyme PRMT5 (protein arginine methyltransferase 5) are associated with aggressive growth of the highly invasive brain cancer glioblastoma multiforme.

Study Details

PRMT5 is an enzyme that alters the structure of chromatin to suppress the transcription of genes and the production of proteins. To conduct their study, the investigators used tumor tissue from patients, cell lines, and an animal model.

PRMT5 was found to be selectively overexpressed in glioblastoma, and the degree of expression correlated with cell growth and patient survival. In patients with glioblastoma, PRMT5 expression levels in tumors were significantly associated with lower overall survival. Patients with high PRMT5 tumor expression had shorter overall survival (108 days) compared to patients with medium expression (277 days) and low expression (726 days).

Possible Therapeutic Target for Glioblastoma

This study showed that inhibiting PRMT5 significantly improved survival in an animal model of glioblastoma multiforme. Blocking the enzyme inhibited the growth, proliferation, and migration of glioblastoma multiforme cells in laboratory studies, and it increased the number of cancer cells that died by apoptosis.

“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,” said cocorresponding author Robert A. Baiocchi, MD, PhD, Associate Professor of Medicine and a hematologist at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

“Our analyses also helped us identify PRMT5 as a master transcriptional repressor in this disease,” said cocorresponding author Balveen Kaur, PhD, Professor of Neurological Surgery at the OSUCCC – James.

“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 in these patients, so a PRMT5 inhibitor might be particularly important for these patients,” said Dr. Kaur.

Drs. Baiocchi and Kaur are the corresponding authors for the Cancer Research article.

The study was supported by grants from the NIH/National Institute of Neurological Disorders and Stroke, The Ohio Cancer Research Associates, V Foundation, 2009 AACR-National Brain Tumor Society Fellowship, and the European Society of Hematology/American Society of Hematology.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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