VCP protein inhibitor found to help virus kill liver tumors

(Medical Xpress)—A team of researchers with members from several institutions in China has found that combining a VCP protein inhibitor with a virus that naturally targets liver cancer tumors made the virus much more potent. In their paper published in the journal Science Translational Medicine, the group describes their search for a way to improve the cancer fighting abilities of a natural virus, the protein inhibitor they found, and how well the two work together to kill cancer cells.

As scientists seek ways to prevent and treat cancer, they sometimes look for natural remedies, including viruses—some actually target and kill cancer cells and are called oncolytic viruses. One such virus, called simply M1, has been found to target hepatocellular carcinoma (HCC) cells which are involved with liver cancer, the second leading cause of cancer deaths in men. M1 is carried by mosquitoes and causes a minor horse illness. But it also seeks out HCC cells and kills them.

Unfortunately, its potency, like other oncolytic viruses, is too low to be of much use as a cancer treatment—it does not kill enough cancer cells to slow tumor growth. But it is good at seeking out HCC cells, which is why the team in China embarked on a study of small molecules that might help M1 kill more cancer cells. They looked at over 350 of them and found that one, Eeyarestatin I, which normally serves to inhibit the production of the protein VCP, had the effects the team was looking for. They created a compound that contained both the virus and the small molecules and found that when it was introduced into cancer cultures, M1 became approximately 3,600 times more potent.

The team next inoculated mice models and found that the M1 virus bolstered with Eeyarestatin I caused tumors to shrink, and in so doing, increased survivability. The team also tested the mix on monkeys and found nearly the same results. They have submitted a request to start a clinical trial for the compound and expect to begin testing in humans sometime next year.