Onalespib May Be an Effective Treatment for Glioblastoma

Vinay PuduvalliThe targeted therapy onalespib has shown effectiveness in preclinical studies of glioblastoma by researchers at the OSUCCC – James. The findings suggest that the targeted inhibitor is long-lasting, crosses the blood-brainbarrier and is more effective when combined with temozolomide, a chemotherapy drug used for brain-tumor treatment.

Onalespib inhibits a protein called HSP90, a molecule that helps newly made protein molecules fold into their functional form. A large number of receptor and DNA-damage-response proteins require HSP90 to achieve functional conformation. In cancer cells, HSP90 expression can be 10 times higher than in normal cells.

This study showed that onalespib blocked HSP90 activity, which reduced expression of cell-survival proteins such as AKT and endothelial growth factor receptor in glioma cell lines and in glioma stem cells obtained from patient tumors. This, in turn, reduced cancer cell survival, proliferation, invasion and migration.

In animal models of glioblastoma (GBM), the agent crossed the blood-brain barrier and was most effective at improving survival in combination with temozolomide.

“Our findings suggest that onalespib can efficiently breach the blood-brain barrier better than other HSP90 inhibitors, and that, in combination with chemotherapeutic temozolomide, could be an exciting new therapy for GBM,” says principal investigator Vinay Puduvalli, MBBS, professor and director of the Division of Neuro-Oncology at Ohio State and a clinician-researcher at the OSUCCC – James.

“Based on the results of this study, we have generated a clinical trial that will determine whether onalespib in combination with standard therapy is safe and effective in patients with newly diagnosed glioblastoma,” he says.

Glioblastoma is the most common form of brain cancer, with more than 12,000 new cases expected in 2017. It remains incurable, with overall survival averaging 16-18 months.

Published in the journal Clinical Cancer Research.

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