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An inexpensive "orphan drug" used to treat sleep disorders appearsto be a potent inhibitor of cancer cells, according to a new study led by scientists at FredHutchinson Cancer Research Center. Their novel approach, usinggroundbreaking technology that allows rapid analysis of the genome,has broad implications for the development of safer, more-effectivecancer therapies. The findings are published in the Proceedings of the National Academy of Sciences. A research team led by corresponding author Carla Grandori, M.D.,Ph.D., an investigator in the Hutchinson Center's Human BiologyDivision, used a high-speed robotic technology calledhigh-throughput screening and a powerful genetic technique calledsiRNA gene silencing to uncover fatal weaknesses in cancer cellsdriven by an oncogene known as "Myc," which is hyperactive in manycancers, including those of the brain, breast, lung, ovary andliver. Myc traditionally has been considered an "undruggable" oncogenebecause it is not readily neutralized by the kind of small, stablemolecule that would work as a cancer drug. Even if such drugsexisted, 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 thosegenes can cripple the cancer's ability to grow." Grandori and colleagues found more than 100 genes which, whenblocked, caused the death of Myc-driven cancer cells but not normalcells. This suggests that each of these genes is a potential targetfor a new, nontoxic cancer therapy. One of these genes, CSNK 1 epsilon, is especially promising. Notonly does silencing it kill cancer while sparing normal tissue, butan inhibitor for the enzyme it produces already exists: a compoundthat originally was developed to modulate sleep cycles. "It had been sitting on a shelf for years, like the thousands ofother 'orphan' drugs that are abandoned when they prove ineffectivefor their intended use," Grandori said. With a simple, five-minute web search, she purchased the compoundonline and designed an experiment to test its potential. She implanted special laboratory mice with Myc-drivenneuroblastomas (a deadly cancer of the nervous system that oftenstrikes children), and treated half of them with the new compound.The untreated mice quickly died of their tumors, but the treatedmice thrived and their neuroblastomas shrank away. "It is possible that the next great breakthrough in cancer therapyis already out there, sitting on a shelf, hiding in plain view,"said Grandori, who is also a research associate professor anddirector of the Quellos High Throughput Screening Core at theUniversity of Washington Department of Pharmacology. Grandori feels that the combination of high-throughput screeningand siRNA silencing has the potential to radically change the waycancers are treated. "We've barely scratched the surface," she said. "These techniquesare incredibly powerful, but they're new and not widely known.There are thousands of researchers who could apply this approach totheir work. In the right hands, it could speed up the developmentof new cancer therapies a thousand-fold." Additional References Citations. I am an expert from autoaircondenser.com, while we provides the quality product, such as Volkswagen Evaporator Manufacturer , Auto Air Conditioning Evaporator Manufacturer, Honda Condenser,and more.
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