'Orphan drug' could be new weapon to fight cancer
Washington: An inexpensive ‘orphan drug’, which is used to tackle sleep disorders, could be a potent inhibitor of cancer cells, a new study has suggested.
The study used groundbreaking technology, allowing rapid analysis of the genome and has been claimed to have broad implications for the development of safer, more-effective cancer therapies.
The team which included corresponding author Carla Grandori, M.D., Ph.D., an investigator in the Hutchinson Centre’s Human Biology
Division, used a high-speed robotic technology called ‘high-throughput screening’ and a powerful genetic technique called ‘siRNA’ gene silencing to uncover fatal weaknesses in cancer cells driven by an oncogene known as "Myc" .
"Myc" is known to be hyperactive in many cancers, including those of the brain, breast, lung, ovary and liver.
Traditionally, it has been considered an "undruggable" oncogene because it is not readily neutralized by the kind of small, stable molecule that would work as a cancer drug.
And even if such drugs existed, they would likely disable ‘Myc’ in normal cells as well, which would create toxic side effects.
"Fortunately, Myc-driven cancer cells have an Achilles heel," Grandori said.
"Their rapid growth and division damages their DNA, and they rely on other genes to repair that damage. Disabling those genes can
cripple the cancer`s ability to grow," she said.Grandori and colleagues have found more than 100 genes which, when blocked, caused the death of Myc-driven cancer cells but not normal cells.
This revealed that each of these genes is a potential target for a new, nontoxic cancer therapy.
One of these genes, CSNK 1 epsilon, is especially promising.
"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," Grandori said.
With a simple, five-minute web search, she was able to purchase the compound online and designed an experiment to test its potential.
She implanted special laboratory mice with Myc-driven neuroblastomas (a deadly cancer of the nervous system that often strikes children), and then treated half of them with the new compound.
The untreated mice quickly died of their tumors, but the treated mice thrived and their neuroblastomas shrank away.
"It is possible that the next great breakthrough in cancer therapy is already out there, sitting on a shelf, hiding in plain view," said Grandori.
Grandori insists that the combination of high-throughput screening and siRNA silencing has the potential to radically change the way cancers are treated.
"We`ve barely scratched the surface," she said.
"These techniques are incredibly powerful, but they`re new and not widely known. There are thousands of researchers who could apply
this approach to their work. In the right hands, it could speed up the development of new cancer therapies a thousand-fold," she added.
The study has been published in the Proceedings of the National Academy of Sciences.