After screening nearly 1,300 chemical compounds, scientists have identified a number of drugs in use today that may in stop the growth of neural stem cells, including cancerous populations. The finding, reported in this week's issue of Nature Chemical Biology, opens up the possibility of using drugs already available to battle brain tumors, which kill an estimated 13,000 people in the U.S. yearly.

"A lot of the receptors for those drugs were thought to be exclusively expressed in mature cells in the central nervous system," says study co-author Peter Dirks, a neurosurgeon and researcher at The Hospital for Sick Children's Brain Tumor Research Center in Toronto, "They may have the same function on stem cells as they do on the mature cells," which makes them candidates for treating brain cancer. Dirks and his team found 160 compounds that interfered with the development and proliferation of neurospheres—clusters of cells in different stages of differentiation, ranging from stem cells to cells well on their way to becoming neurons or glia (cells that support and insulate neurons). The researchers then tested the drugs both in vitro, with cells derived from an embryonic mouse brain, human brain tumor cells and with cancer cells from knockout mice, which were genetically predisposed to develop brain tumors.

Several of the prescreened drugs seemed to inhibit tumor growth in the human and mouse cancer cells as well as in the knockout mice. "Some of the drugs were quite selective for the human cancer cells versus the normal human cells," Dirks says, "suggesting there may be some window of therapeutic opportunity." The drugs are already being used to treat other disorders.

Among them: butaclamol is used to inhibit receptors for dopamine (a neurotransmitter active in the brain's reward and pleasure systems) and as an antipsychotic for schizophrenics. Ifenprodil acts on the amino acid NMDA, the receptors of which play a role in long-term memory. It is often prescribed to relax cerebral blood vessels after a stroke. Carbetapentane is a cough suppressant that heightens the activity of opioid receptors, which are active in pain relief. The myriad actions of the drugs tested, Dirks notes, "suggests the incredible diversity of pathways that might be regulating neural stem cells."

According to Dirks, now that the preliminary screen for candidate therapies has been performed, his group will take the most promising and determine whether they can inhibit the proliferation and growth of human tumor cells engrafted into the brains of mice. "We've cured cancer in the dish many times over, but we need to show this in vivo," says Dirks, who hopes to have the results of the new research by the end of the year.

If those tests are successful, he believes he can move somewhat swiftly to human trials, especially since terminal brain cancer patients are often more willing to engage in new, unproved treatment options. "Because we know that all the conventional therapies eventually fail," Dirks explains, "many patients do go on investigational therapy."

1 Comments

1. 1. litarose 03:47 PM 7/5/08

   I have a 47 yr. old son with brain tumor/cancer. It is an astrocytoma. He has had surgery and couldn't take it all. He has had radiation. He is a drug addict, (crack cocaine). He has been in kidney failure previously He has been in 6 different rehabs, gone to 12 step programs and nothing has worked so far. His surgeon says that the tumor could have contributed to his addiction, it is slow growing and they feel he has had it since birth. When he was 12 he had a large flat tumor removed from two layers of his skull. At that time they did not find this tumor. He also has had sex addiction problems. He is now down to using twice a week, once he was off for years when he was in jail. (maybe?) I just took his car keys, ATM card and am keeping him in one room hoping I can contain him, but when he wakes up from this after using for 3 days and losing 25 lbs. who knows if I can keep him from leaving. Is there any help anywhere, are there clinical trials that he could be enrolled in or is it too late for him? HELP
   
   litawatson@aol.com

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