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Drug found to relieve side effects of cancer treatments

Updated:
WASHINGTON (AP) -- An experimental drug may relieve some of the
miserable side effects of cancer treatment, allowing stronger doses
of chemotherapy and radiation, researchers say. Ironically, the
drug works by briefly blocking a gene that is a natural defense
against cancer.

Although the drug has been used only in mice, researchers at the
University of Illinois at Chicago are preparing to test it in
baboons and hope to have it ready for human tests in about a year.

A report on the drug study in mice appears Friday in the journal
Science.

Andrei V. Gudkov, lead author of the study, said that if the
drug works in humans, it may be possible to give more vigorous
radiation and chemotherapy treatments for cancer without an
increase in the 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."

"This is an interesting and novel finding that could be very
important in cancer treatment," said Dr. Carlos Cardon-Cardo,
director of molecular pathology at the Memorial Sloan-Kettering
Cancer Center in New York.

Cardon-Cardo said that if side effects of cancer treatment could
be eliminated or controlled, "it would allow us to give higher
doses and more effective doses" of radiation and anti-tumor
chemicals.

He cautioned, however, that the experimental drug has so far
been tested only in mice and its effects in humans is still
unknown. Also, Cardon-Cardo said researchers will have to carefully
evaluate the drug's long-term influence on healthy cells.

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

The job of p53 is to identify cells with damaged genes and 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, anemia, 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.

A hopeful sign, he said, is that there were no new cancers among
the treated mice, a suggestion that p53 resumed its job of killing
potentially cancerous cells.

Gudkov said it appears that by the time the effects of the
pifithrin wears off, many cells damaged by radiation or
chemotherapy had repaired themselves. P53 then acted only against
those cells beyond repair, leaving the other cells alone, he said.

He said the drug could be used only in cancer patients whose
tumors have a missing or mutated p53 gene, a characteristic of
about half of all cancers.

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




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