Low Dose of Targeted Agent May Enhance Cancer-Destroying Virus Treatment

Administering low doses of the targeted agent bortezomib with a cancer-killing virus has the potential of enhancing the effectiveness of the virus as treatment for cancer with little added toxicity. This, according to researchers from the Ohio State University Comprehensive Cancer Center (Columbus, USA)-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James). These new findings support the testing of this combination therapy in a clinical trial.

Viruses that are devised to destroy cancer cells—oncolytic viruses—have demonstrated potential in clinical trials for the treatment of brain cancer and other solid tumors. This cell and animal research suggests that mixing low doses of the drug bortezomib with a specific oncolytic virus might substantially enhance the capacity of the virus to kill cancer cells during therapy.

The research was published online May 9, 2014, 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,” said lead investigator Balveen Kaur, PhD, 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 [US] Food and Drug Administration, a clinical trial could be done relatively quickly to test the effectiveness of the drug-virus combination.”

Bortezomib suppressed the activity of proteasomes, structures in cells that break down and recycle proteins. Prof. Kaur noted that blocking these “cellular recycling plants” triggers 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, the investigators used a herpes simplex virus-type 1 oncolytic virus. Key technical findings include: (1) One of the overexpressed heat-shock proteins, HSP90, facilitates oncolytic virus replication, enabling the virus to kill more tumor cells; (2) in a glioma model, the combined treatment suppressed tumor growth by 92% in relation to controls and improved survival (six of eight tumors had entirely regressed by day 23 after treatment); (3) lastly, 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,” Prof. Kaur concluded. “It offers a novel therapeutic strategy that can be rapidly translated in patients with various solid tumors.”

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Ohio State University Comprehensive Cancer Center