A drug that kills cancer cells as they try to divide has shown "dramatic" results in early research, paving the way to potentially curative treatments.
In the laboratory, the drug, OTS964, eradicated aggressive human lung cancers transplanted into mice while producing few side-effects.
The findings raise hopes of developing a revolutionary pill or injection that is effective against a wide range of diseases, including breast, brain, liver and bladder cancer, as well as some types of leukaemia.
Human trials of OTS964 are expected to start by autumn next year.
US lead scientist Professor Ysuke Nakamura, from the University of Chicago, said: “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.
“We initially screened 300,000 compounds and then synthesised 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,” he said.
The drug works in a unique way by blocking the action of a protein, TOPK, that is essential for successful cell division and is over-produced in many types of cancer.
“Without TOPK the cells can’t seem to divide; they can’t make the break,” said Prof Nakamura.
“They can’t complete the process. 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.”
Initial studies of an earlier version of the treatment found it effectively killed cancer cells — but at an unacceptable price. It also disrupted the generation of new red and white blood cells, causing anaemia and damaging the immune system. It also increased the risk of blood clots by boosting numbers of platelets.
These hurdles were overcome by encapsulating the drug in microscopic bubbles called liposomes, which suppressed blood toxicity.
In the mouse tests, aggressive human lung tumours were allowed to grow until they reached 150 cubic millimetres, about the size of a raisin.
Injections of OTS964 twice a week for three weeks caused the tumours to shrink rapidly and continue shrinking even after treatment stopped. The cancer completely disappeared in five of the six mice, with no detectable side effects.
Larger doses of the drug taken by mouth also proved effective in another group of mice. In all six animals, the tumours vanished.
Although these mice had low white blood cell counts after treatment, they recovered within two weeks.
Prof Nakamura described the results, published in the journal Science Translational Medicine, as “dramatic”.
He added: “It is rare to see complete regression of tumours in a mouse model. Many drugs can repress the growth, but it is uncommon to see them eradicated. This has rarely been reported.”
In studies of the drug’s effect on cells growing outside the body, the scientists videoed its cancer-killing ability in action.
The TOPK target protein appears to play a central role in cytokinesis, the final stage in cell division, the scientists reported. They pointed out that the protein’s gene was frequently “upregulated” — extra-active — in breast, brain, liver, and bladder cancers as well as other solid tumours and certain types of leukaemia blood cancer.
This raised the exciting possibility of the drug being effective across multiple cancer types.
Professor Peter Parker, an expert in cell signalling at Cancer Research UK, said: “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.”
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