Protein inhibitor may be a game changer for oncolytic therapies

virus cell
The first and only FDA-approved oncolytic drug, Amgen's Imlygic, works as a single therapy for a niche group of patients. Sun Yat-Sen University researchers discovered a compound that promotes the cancer-killing ability of oncolytic viruses, which could make them effective for a broader patient population.

Oncolytic viruses have been lauded as “the next major breakthrough” in cancer treatment, but have had limited success in human trials. Chinese researchers have landed on a compound that could boost the cancer-killing ability of these viruses.

These viruses can be naturally occurring or genetically engineered, and they target and kill cancer cells while leaving healthy cells unharmed. Researchers at Sun Yat-Sen University in China screened 350 small molecules in search of one that might promote the anti-tumor effects of the cancer-killing virus M1. A mosquito-borne virus, M1 selectively kills liver cancer cells thanks to inherent flaws in the cancer’s antiviral defense.

They found that combining M1 with an inhibitor of the protein VCP dialed up its cancer-killing activity as much as 3,600-fold in cultured hepatocellular carcinoma. The combination also shrank tumors and improved survival in mouse models, and was safe and well tolerated in nonhuman primates. The research was published in the journal Science Translational Medicine.

Amgen’s Imlygic was the first oncolytic drug to earn FDA approval, back in 2015. It is approved as a monotherapy for the treatment of inoperable melanoma, but the Big Pharma is testing it in combination approaches in a bid to widen the patient population for the drug.

Competitors are jumping into the oncolytic virus arena. In July 2016, Cambridge, Massachusetts-based Oncorus reeled in $57 million to develop its oncolytic treatments for aggressive brain cancers. And this year, Japan’s Oncolys BioPharma started phase 2 trials of its Telomelysin in patients with advanced melanoma (PDF), as well as a phase 1 trial that will gauge how the drug fares against esophageal cancer (PDF) when administered alongside radiotherapy.

Promoting M1’s efficacy is an obvious benefit of using the VCP inhibitor, but the scientists at Sun Yat-Sen University also noted that tumor cells with high VCP expression were more sensitive to the combination treatment. Therefore, VCP expression might someday be used to identify which patients would benefit most from the combo.