Shelved sleep disorder drug neutralises 'undruggable' cancer cells

In collaboration with the Press Association

US scientists have used an abandoned sleep disorder drug to target a cancer protein in mice that was previously considered 'undruggable'.

The drug's potential was identified after a research team at the Hutchinson Center's Human Biology Division used a technique called siRNA gene silencing, paired with a robotic technology known as high-throughput screening, to selectively knock out different processes in cancer cells driven by a faulty protein called Myc.

The research is published in the Proceedings of the National Academy of Sciences.

Myc is an 'oncoprotein', essential for normal growth, but able to cause cancer if the gene that makes it becomes damaged - as is the case in a wide range of cancers, including many brain, breast and lung tumours.

Myc was thought to be 'undruggable' because it is not easily targeted by the sort of stable, small molecules that work as cancer drugs.

Even if such drugs could be developed, they could cause serious side effects because of their effect on normal cells.

Dr Carla Grandori, who led the research, said the rapid growth of Myc-driven cancer cells damages their DNA, so they become dependent on other processes to fix the damage. Such processes creates an 'Achilles heel' that can be exploited, she said.

The researchers found more than 100 genes that affected Myc-driven cancer cells when they were blocked, without affecting normal cells, raising the possibility that non-toxic cancer therapies could be used to target each of these genes.

The researchers think targeting one specific gene, CSNK 1 epsilon, could be especially fruitful. A drug to target this gene already exists and was originally developed to modulate sleep cycles.

The researchers used the drug to treat mice with Myc-driven neuroblastomas (a cancer of the nervous system), and found that it shrank the tumours.

"It had been sitting on a shelf for years, like the thousands of other 'orphan' drugs that are abandoned when they prove ineffective for their intended use," said Grandori. "It is possible that the next great breakthrough in cancer therapy is already out there, sitting on a shelf, hiding in plain view."

Grandori believes that the high-throughput gene silencing methods her team used had great potential and could be used by thousands of researchers to hasten the development of new cancer therapies.

Dr Laura McCallum, science information manager at Cancer Research UK, said: "This early research in mice highlights how technology is speeding up progress in understanding cancer, but much more work is needed to see if this drug could actually help treat people with the disease.

"The idea that orphan drugs - medicines that don't have a current clinical use - could be developed and tested to treat cancer is not a new one. For example our researchers recently explored the use of an orphan drug for rare childhood cancers."

Copyright Press Association 2012

References

  • Toyoshima, M. et al (2012). Functional genomics identifies therapeutic targets for MYC-driven cancer Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1121119109