OTS964 targets TOPK, a protein that is produced by a wide range of human cancers and is believed to promote tumor growth. High TOPK expression correlates with poor prognosis in patients with breast and lung cancer.

Initial studies of the drug, and a precursor called OTS514, found that they were effective in killing cancer cells but could also disrupt the production of new red and white blood cells, causing mild anemia and increasing the risk of infection. At the same time, the drugs increased the production of platelets, which help in blood clotting.

When the researchers encapsulated the drugs in liposomes—microscopic bubbles similar to a cell membrane that are commonly used to transport drugs within the body—the drug no longer caused this decrease in red and white blood cells. This approach “completely eliminated the hematopoietic toxicity,” the researchers wrote.

They tested OTS964 alone and in liposomes in mice with a highly aggressive human lung tumor known as LU-99. They allowed the tumors to grow to 150 cubic millimeters, and then administered the drug intravenously to six mice, twice a week for three weeks. The tumors shrank rapidly and continued to shrink even after treatment stopped. In five of the six mice, the tumors completely disappeared—three within 25 days of the first treatment and two within 29 days. Mice that received the liposome-coated drug had no detectable toxicity.

The drug also proved effective when taken in larger doses by mouth. Six mice with LU-99 lung tumors were fed 100 milligrams per kilogram of OTS964 every day for two weeks. Again, continuous tumor shrinkage was observed after the final dose of the drug. In all six mice, the tumors completely regressed. All of the mice had low white blood cell counts after treatment, but they recovered within two weeks.

Although this was a small study, the outcome was dramatic. Seeing these results was a “quite exciting moment,” said Nakamura, who stepped down from his role as director in the Japanese Government’s Office of Medical Innovation to join the faculty at UChicago in April 2012. “It is rare to see complete regression of tumors in a mouse model,” he said. “Many drugs can repress the growth but it is uncommon to see them eradicated. This has rarely been reported.”