A new drug known as OTS964 can eradicate aggressive human lung cancers that were transplanted into mice, according to a new report. The drug inhibits the action of a protein that is overproduced by several tumor types, including lung and breast, but is rarely expressed in healthy adult tissues. Without this protein, cancer cells fail to complete the cell-division process and die.

When taken by mouth, the drug was well tolerated with limited toxicity. An intravenous form, delivered within a liposome, was just as effective with fewer side effects. Both approaches, described in Science Translational Medicine (2014; doi:10.1126/scitranslmed.3010277), led to complete regression of transplanted tumors.

“We identified the molecular target for this drug 10 years ago, but it took us nearly a decade to find an effective way to inhibit it,” said study author Yusuke Nakamura, MD, PhD, professor of medicine at the University of Chicago in Illinois and deputy director of the University’s Center for Personalized Therapeutics. “We initially screened 300,000 compounds and then synthesized more than 1,000 of them, and found a few that were likely to work in humans. We focused on the most effective. We think we now have something very promising.”

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OTS964 targets TOPK (T-lymphokine-activated killer cell-originated protein kinase), which is 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 they were effective in killing cancer cells. But they could disrupt the production of new red and white blood cells, causing hematopoietic toxicity such as 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, which are microscopic bubbles similar to a cell membrane, 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, and then, after treating the mice with OTS964, the tumors shrank rapidly and continued to shrink even after treatment stopped. In five of the six mice, the tumors completely disappeared in less than 1 month. Mice that received the liposome-coated drug had no detectable toxicity.

The drug also proved effective when taken in larger doses by mouth.

Seeing these results was a “quite exciting moment,” said Nakamura. “It is rare to see complete regression of tumors in a mouse model. Many drugs can repress the growth, but it is uncommon to see them eradicated. This has rarely been reported.”

TOPK may provide a good drug target for several types of cancer, including several types of solid tumors and certain types of leukemia. The researchers are working with oncologists to begin a phase 1 clinical trial as soon as the fall of 2015.