Giving 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 Ohio State University.
The research is published in the journal Clinical Cancer Research.
“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, Professor and Vice Chair of Research, Department of Neurological Surgery and Radiation Oncology, and a member of the OSUCCC – James Translational Therapeutics Program.
“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 oncolytic virus. Key technical findings include:
- One of the overexpressed heat-shock proteins, HSP90, facilitates oncolytic virus replication, enabling the virus to kill more tumour cells;
- In a glioma model, the combination treatment suppressed tumour growth by 92 percent relative to controls and improved survival (six of eight tumours had completely regressed by day 23 after treatment);
- Similar outcomes occurred in a head and neck cancer model.
“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 tumours.”
Source: Ohio State University