A recent study titled “TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis”, published in the journal Science Translation Medicine, showed that in mice models of lung cancer, tumors completely disappeared after the administration of the experimental drug OTS964.
This drug has the capacity to switch off the TOPK protein, involved in tumor growth in a variety of cancers, including lung and breast.
“Without TOPK the cells can’t seem to divide. Instead they remain tethered by a tiny bridge. When that finally breaks apart, they can’t close the membrane. Everything within the cells spills out, they suffer and then die”, study author Professor Yusuke Nakamura explained in a Cancer Research UK press release.
The team of researchers, from the University of Chicago (UC), analyzed 300,000 chemicals that produced over 1,000 compounds, one of which was developed into OTS964.
After successful in vitro experiments, the team tested the investigational drug in mice models carrying human lung cancer cells, intravenously injecting them for three weeks and observing a significant and rapid decrease in tumor load, even after the treatment had been discontinued. Importantly, 5 out of 6 mice had their tumors completely eradicated.
However, intravenous administration of the compound interfered with hematopoiesis, resulting in anaemia and increased risk of infections. To bypass this problem, researchers used liposomes as drug vehicles, which proved to work as effectively as the initial injections but without the deleterious side effects.
“The findings of this early stage study are interesting, and the profound effect on tumour growth in mice shows that switching off TOPK could be a promising approach for treating some cancers in the future. But so far the results have only been shown in cells grown in the lab and in mice, leaving a number of questions unanswered. Piecing together the finer details of how TOPK controls cell division, and the consequences of switching it off, will be crucial before this potential new drug can be taken further into clinical trials,” Professor Peter Parker, a Cancer Research UK expert in cell signaling, added in the press release.
Researchers are now collaborating with UC oncologists, and a Phase-1 clinical trial of OTS964 is expected to commence in late 2015.