Chinese scientists have found a compound that helped a tumor-targeting virus kill liver cancer more effectively while sparing healthy cells, offering new hope for treating the world's second most common cancer killer, according to a study published Wednesday.
A therapy using viruses that selectively kill cancer cells, dubbed oncolytic viruses, is rapidly progressing through clinical evaluation, but the therapeutic efficacy in humans has been less than expected from preclinical studies, according to the study published in the U.S. journal Science Translational Medicine.
Oncolytic virotherapy involving M1 virus, a mosquito-borne pathogen that predominantly causes mild illness in horses, is believed to be a potentially attractive strategy for the treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer.
In order to boost the virus's antitumor effects, Professor Guangmei Yan of Sun Yat-sen University in China and colleagues screened 350 small molecules to identify compounds that can enhance viral killing of cultured HCC cells.
The researchers found that Eeyarestatin I, an inhibitor of the protein VCP, which has been linked to causing malignancy, as the strongest sensitizer for M1 virus, as it increased the potency of the virus by as much as 3,600-fold against the HCC cells.
The dual regimen had no effect on non-cancerous cells, they said.
In multiple mouse models of HCC, M1 together with Eeyarestatin I were found to shrink tumors and significantly prolong survival.
The researchers further demonstrated that the duo was safe and well-tolerated in monkeys.
"We can describe the M1 oncolytic virus as a guided missile that automatically targets tumor cells, and the addition of the VCP inhibitor is just like binding the missile to powerful explosives with the ability of auto-selection," Yan explained to Xinhua.
"The outcome is self-evident with such a strong combination," he said.
Yan said they plan to submit a clinical trial application for the combination therapy strategy in 2018.
"Hepatocellular carcinoma is the second leading cause of cancer-related death in men and claims more than 700,000 lives per year worldwide," their paper wrote. "Our study identifies combined VCP inhibition and oncolytic virus as a potential treatment for HCC and demonstrates promising therapeutic potential."
