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Targeting p53: New compound may help suppress tumors


Persons are more vulnerable to developing tumors when their p53 gene is mutated or inactivated. In fact, half of all human tumors involve mutations in that tumor-suppressing gene. Now, scientists have discovered a chemical compound that restores function to mutant p53 genes in human tumors grown in mice.

Effect of PRIMA-1 on the conformation of mutant p53 proteins. View larger

Researchers in Sweden and Russia have identified a molecule that can restore the p53 gene's ability to induce apoptosis—cell death—and possibly slow the development of tumors. The compound, called PRIMA-1, may prove useful in efforts to develop a new generation of anti-cancer drugs that targets mutant p53 genes.

"The identification of a small molecule able to restore biochemical and biological function to mutant p53, resulting in significant tumor suppression in vivo, opens exciting prospects for future cancer therapy," Klas G. Wiman, of the Karolinska Institute's oncology department in Stockholm, and colleagues write in Nature Medicine.

The researchers started by looking for a chemical compound with low molecular weight that was capable of restoring normal function to mutant p53 genes. They found that PRIMA-1 fit the bill by 'rescuing' p53 mutants. The scientists then conducted in vivo studies in mice, which showed that PRIMA-1 had "an antitumor effect with no apparent toxicity."

More research is needed to investigate the molecular mechanism of how PRIMA-1 reactivates mutant p53 genes to help suppress tumors. Understanding that mechanism may make it possible to design a class of drugs that target different types of tumors.

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Bykov, V.J.N. et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 8, 282-288 (March 2002).

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