THE P53 GENE IS A MOLECULAR policeman. It detects damage in a cell's DNA and keeps the cell from dividing until repairs take place. More than half of all major cancers involve p53 genes that don't work correctly. Now, researchers at Onyx Pharmaceuticals Inc. in Richmond, Calif., are trying to capitalize on that fact. Their idea is to slip an intruder past the disabled policeman and selectively kill cancer cells.
The technique is based on the discovery that adenovirus--a virus that causes mild flu-like symptoms--makes a protein that disables the p53 gene after it enters a cell. Without p53 to interfere, the virus takes over and replicates itself, killing the cell it's in.
For their cancer therapy, Onyx scientists developed an adenovirus that can't make the protein that inactivates p53. In normal cells the virus is harmless: p53 will stop the infected cell from dividing. But in cancer cells that lack a working p53, the virus takes over production. The cancer cells eventually burst and die--releasing lots more of the virus to infect more tumor cells.
Dr. William Gerber, the chief operating officer of Onyx, says that the altered adenovirus is safe and effective in mice. Onyx hopes to begin clinical trials of the drug in people with head and neck tumors next year.