Suncoast Pinellas News
Test Drug Frees Up Anti-Cancer Protein
U-M Comprehensive Cancer Center
The anti-cancer molecule MI-219 binds to another protein, Mdm2. By tying up Mdm2, MI-219 keeps Mdm2 from blocking the action of the cancer-fighting protein p53.
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Published: March 5, 2008
For a decade researchers have been looking for a compound that would keep the p53 gene in the battle against cancer. Scientists at the University of Michigan Comprehensive Cancer Center have cobbled together something they think may be on the right track.
So far, a protein molecule created by Shaomeng Wang and his U-M colleagues, dubbed MI-219, has shown promise in test in animals and human cancer cells in a laboratory dish.
Normal human cells have the p53 gene, which produces a namesake cancer-fighting protein. In almost all types of human cancers, however, the p53 protein isn't able to carry out its tumor-suppressing role.
About half the time the problem is either a mutation in the p53 gene or the complete absence of the gene.
The rest of the time the culprit is another protein, known as Mdm2. The Mdm2 protein inhibits the p53 protein by binding to it.
Wang says MI-219 can re-activate the p53 protein's ability to kill cancerous cells. Unlike other drugs created for this purpose, however, MI-219 can do so without causing damage to the master genetic material DNA and killing normal cells in the process.
"For more than 10 years scientists have searched for ways to block p53 inhibition, but with little success," said Wang, co-director of the molecular therapeutics program at the U-M Comprehensive Cancer Center. "Our study clearly shows that this can be done."
Wang and U-M, it should be noted, own stock in Ascenta Therapeutics, a Pennsylvania-based company that has purchased the rights to develop MI-219.
The U-M group reported on its work with MI-219 in the March 3 online edition of the Proceedings of the National Academy of Sciences.
The U-M team designed MI-219, a relatively small molecule as proteins go, using a computer. In tests of the molecule on animal with tumors that mimic human cancers, MI-219 completely inhibited tumor growth and appeared to cause no toxicity to the animals.
Although these results are encouraging they must be verified through lengthy human clinical trials, Wang cautions. The researchers have not yet set a date for the start of the series of tests.
If these human tests are a success, MI-219 could have another thing going for it as an anti-cancer drug. It can be turned into a pill that cancer patients could take at home. Most cancer-fighting drugs must be administered intravenously at a hospital or treatment center.
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