Researchers have long searched for a novel cancer drug that activates a certain protein to kill tumor cells.
But finding a drug that kills the cancer without causing damage to normal cells has stymied researchers.
Now, researchers at the University of Michigan Comprehensive Cancer Center have designed a small molecule that is highly effective in cell cultures at inhibiting the interaction between this protein, called p53, and another protein that inactivates p53 in cancer. The new molecule is ideal for drug development as it can be given orally as a pill and it appears to be safe for use in animals.
“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, Ph.D., 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.
If clinical trials prove out the drug's promise, it could have potential for treating many different types of cancer. Results of the study appear the week of March 3 in the online edition of the Proceedings of the National Academy of Sciences.
The protein p53, which normally helps suppress tumors, is inactivated in almost all human cancers. About half the time, p53 does not do its job because the gene that holds the protein is mutated or missing altogether. The other half of the time, another protein, called human MDM2, is the culprit. It binds to p53 and inhibits the tumor suppressor function of p53, promoting cancer development.
Using a computer-assisted approach, U-M researchers designed a small molecule, called MI-219, that is highly effective in blocking the interaction of MDM2 and p53. MI-219 specifically kills tumor cells by harnessing the power of p53. In animal models of human cancer, MI-219 completely inhibited tumor growth and appeared to cause no toxicity to animals.