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Big Hope For Cancer Patients In 'Small Molecules'

by Dr. Sunil Shroff on  March 4, 2008 at 5:11 PM Cancer News   - G J E 4
Big Hope For Cancer Patients In 'Small Molecules'
A spate of studies are going on in cancer;the latest one has its promise in 'small molecules' developed by the researchers of University of Michigan.
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The researchers say that the new molecule called MI-219 is ideal for drug development given that it can be administered orally as a tablet, and has appeared to be safe for use in animal studies.

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"For more than 10 years scientists have searched for ways to block p53 inhibition, but with little success. Our study clearly shows that this can be done," says study author Shaomeng Wang, Warner-Lambert/Parke-Davis Professor in Medicine at the U-M Medical School and co-director of the molecular therapeutics program at the U-M Comprehensive Cancer Center.

A report on the study's findings, published in the online edition of the Proceedings of the National Academy of Sciences, suggests that the new molecule may have the potential to treat many different types of cancer if human trials also show promising results.

In almost all human cancers, the protein p53, which normally helps suppress tumours, is inactivated. The gene does not do its job almost half the time because the gene that holds it is either mutated or missing altogether; while the other half of the time, another protein called human MDM2 binds to p53 to inhibit its tumour suppressor function.

The U-M team used a computer-assisted approach to design the MI-219 molecule, which they say is highly effective in blocking the interaction of MDM2 and p53. According to the researchers, MI-219 specifically kills tumour cells by harnessing the power of p53.

In animal models of human cancer, MI-219 completely inhibited tumour growth without cause toxicity.

"Many traditional cancer drugs also activate p53 but they do so by causing DNA damage. They kill not only tumour cells but also normal cells, thus having severe side effects. MI-219 is unique in that it is designed to activate p53 without causing DNA damage, specifically killing tumour cells. Indeed, MI-219 is highly effective in inhibiting tumour growth, and even inducing tumour regression, but it has caused no toxicity to animals at efficacious doses," says Wang, professor of internal medicine and pharmacology at the U-M Medical School and professor of medicinal chemistry at the U-M College of Pharmacy.

The researchers say that MI-219 can be developed as a pill so that patients can take orally, rather than the traditional chemotherapy drugs that must be given intravenously at a hospital or cancer centre.

Wang, however, cautions: "While promising in pre-clinical studies, MI-219 needs to be evaluated in human clinical trials for its safety and efficacy for cancer treatment since it is a brand new drug."

Source: ANI
SUN/L
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