New Anti-Cancer Drug Shows Promising Results With Low Toxicity
By C. Rajan, contributing writer
Researchers at the University of Chicago have reported ‘dramatic’ anti-cancer activity of a new drug, OTS964, which was able to completely eliminate aggressive human lung cancers transplanted into mice — and with minimal side effects. The drug inhibits the activity of a key protein involved in the cell division process, thus preventing the cancer cells from replicating.
OTS964 was tested both as a pill and an injection, and both forms of administration were found to be equally effective in bringing about complete regression of transplanted tumors. The researchers plan to initiate the Phase 1 clinical trial of OTS964 in humans by fall 2015.
OTS964 works by targeting and blocking the activity of TOPK (T-lymphokine-activated killer cell – originated protein kinase), a protein that is essential for tumor growth through cell division and is over-expressed in many types of cancer. While this study focused on lung cancers, targeting TOPK can lead to treatments for breast, brain, liver and bladder cancer, as well as some types of leukemia.
"We identified the molecular target for this drug ten years ago, but it took us nearly a decade to find an effective way to inhibit it," said lead author Yusuke Nakamura, MD, PhD, professor of medicine at the University of Chicago 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."
During the initial studies with the drug, the researchers observed excellent cancer killing ability. However, the drug was also found to affect the production of new white and red blood cells leading to the undesirable side effects of mild anemia and increased risk of infection.
The researchers solved this issue of hematopoietic toxicity by encapsulating the drug in microscopic bubbles called liposomes that transport drugs within the body. The liposome-encapsulated drug no longer caused decreases in red and white blood cells and showed few side effects in the mice.
Dr. Nakamura described the results as “dramatic” and added, "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."
The research was published last week in Science Translational Medicine titled, “TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis.”