Making Cancer Drugs Gentler

Some of the serious side effects of cancer treatments can be prevented by a drug that, ironically, briefly blocks the body's natural defense against cancer, according to a study in the journal Science.

The experimental drug has been used only in mice, but researchers at the University of Illinois at Chicago said it should be ready for human tests in about a year.

If the drug works in humans, said Andrei V. Gudkov, then it would mean more vigorous radiation and chemotherapy treatment of cancer without an increase in side effects that cause such misery for patients.

"Cancer treatment is usually such a pain that people feel bad not only physically, but also emotionally and psychologically," said Gudkov, a molecular genetics researcher at the university. "Making this treatment more bearable would be a tremendous advantage for these patients."

Gudkov said the drug works by temporarily knocking out a gene called p53 that normally protects the body against flawed cells that might become cancer.

The job of p53 is to identify cells with damaged genes and then to cause those cells to kill themselves.

When patients undergo radiation or chemotherapy, the treatment often damages cells that are then forced by p53 to commit suicide.

The problem, said Gudkov, is that p53 sometimes acts so powerfully that it kills cells that are only slightly damaged and that, given a chance, could recover.

"P53 pushes a lot of damage cells to die just as a preventative measure," he said. "It kills too many cells. It kills cells that may not need to die."

It is the death of these damaged cells that causes many of the side effects of cancer treatment -- nausea, hair and weight loss and a weakened immune system.

Gudkov and his team identified a drug, called pifithrin, that blocks the action of p53 for about three hours.

Using mice that had tumors, the researchers injected pifithrin in some animals and not in others. All the animals were then subjected to radiation typical of a cancer treatment.

Gudkov said those mice with blocked p53 gene tolerated the radiation much better than the other animals. In one test, all 30 treated mice lived 8 1/2 months, while only five of an untreated group survived that long.

When the drug wore off, he said, the p53 gene was once more active, but by then the damaged cells had repaired themselves and were not forced to commit suicide. The gene acted only on cells that were beyond repair.

The drug has no effect on the cancer itself, said Gudkov, since most cancers lack the p53 gene. The drug could used only in patients whose tumors did not have the gene, he said.

Gudkov said pifithrin will be tested on baboons before it is tested on humans. The baboon work is just getting started, he said.

Written By Paul Recer