Expanding Efficacy

Low Doses of Targeted Drug Might Improve Cancer-Killing Virus Therapy

Balveen KaurGiving low doses of a particular targeted agent with a cancer-killing virus might improve the effectiveness of the virus as a treatment for cancer, according to a study led by researchers at the OSUCCC – James.

Viruses that are designed to kill cancer cells—oncolytic viruses—have shown promise in clinical trials for treating brain cancer and other solid tumors. This cell and animal study suggests that combining low doses of the drug bortezomib with a particular oncolytic virus might significantly improve the ability of the virus to kill cancer cells during oncolytic virus therapy.

“These findings pave the way for a treatment strategy for cancer that combines low doses of bortezomib with an oncolytic virus to maximize the efficacy of the virus with little added toxicity,” says principal investigator Balveen Kaur, PhD, professor and vice chair of research in the Department of Neurological Surgery at Ohio State, and an associate director for shared resources at the OSUCCC – James. “Because bortezomib is already approved by the Food and Drug Administration, a clinical trial could be done relatively quickly to test the effectiveness of the drug-virus combination,” Kaur says.

Bortezomib inhibits the activity of proteasomes, structures in cells that break down and recycle proteins. Kaur notes that blocking these “cellular recycling plants” activates a cellular stress response and increases the expression of heat shock proteins. This reaction, which can lead to bortezomib resistance, makes the cells more sensitive to oncolytic virus therapy with little additional toxicity.

For this study, Kaur and her colleagues used a herpes simplex virus-type 1 (HSV-1) oncolytic virus.

“To our knowledge, this study is the first to show synergy between an oncolytic HSV-1-derived cancer-killing virus and bortezomib,” Kaur says. “It offers a novel therapeutic strategy that can be rapidly translated in patients with various solid tumors.”

Published in the journal Clinical Cancer Research.

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