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Skin cream tackles skin cancers in mice
Compound acts by rejuvenating ‘the guardian of the genome’.
A skin cream that can hyperactivate the body's natural DNA repair mechanisms has been shown to protect mice from skin cancer, and to reduce the growth of cancers already present. If the compound does the same for humans, it could one day be added to sunscreen as a cancer-fighting ingredient.
The active component of the cream, called CP-31398, works by reactivating disabled forms of a natural tumour-suppressing protein called p53. Nicknamed ‘the guardian of the genome’, p53 controls several important cellular functions, including the repair of damaged DNA, cell division and a genetically encoded auto-destruct pathway called apoptosis that kills unhealthy cells.
The p53 gene is mutated in over half of all human cancers. For that reason, pharmaceutical companies have been hunting compounds that can protect or restore p53 activity, in the hope that these might prevent or treat cancer.
In 1999, researchers at Pfizer showed that CP-31398 restores normal activity to mutated p53 proteins in cell cultures (although how exactly it works is a mystery)1. Mohammad Athar, a biochemist at the University of Alabama in Birmingham, went on to test the compound in live animals.
Athar and his colleagues slathered the compound onto the skin of hairless mice, and then exposed the mice to ultraviolet (UV) light twice a week for 35 weeks. At the end of the experiment, mice treated with CP-31398 had seven tumours on average; control mice that did not receive the drug had 16.
The tumours that did grow on treated mice were roughly a sixth the size of tumours in control mice. And, Athar and his colleagues found, the compound slowed the growth of preexisting skin tumours. The results are published this week in the Journal of Clinical Investigation 2.
Repair cream
“I think the results of this preclinical study look promising,” says Wafik El-Deiry, a cancer biologist at the University of Pennsylvania School of Medicine in Philadelphia. “If the compound survives subsequent testing it could be used as an additive to sunscreen.”
CP-31398 is not the first skin treatment that has been shown to repair cellular damage from sun exposure. Lotion containing fragments of DNA can ward off precancerous skin lesions in mice (see DNA-boosted sunscreen may fight cancer), and a salve containing a DNA repair protein reduces the number of skin tumours in people with a genetic defect in this DNA repair system. One important next step will be to compare how the cancer-fighting properties of CP-31398 compare not only to these experimental alternatives but also to the UV-blocking properties already in sunscreens, El-Deiry says.
And before CP-31398 can be used in humans, it will have to be tested for safety and efficacy. Athar says that he has not observed negative side effects of the drug in mice, but previous work suggests that too much p53 can cause premature ageing (see Cancer-proof mice age prematurely). CP-31398 restores mutant p53 proteins to their normal function, but it is not yet clear whether the drug boosts p53 activity beyond that found in a typical cell. Athar says that so far his lab has found no evidence that CP-31398 enhances p53 activity beyond normal levels.
It is also not clear whether CP-31398 will be active against other forms of cancer. Different cancer-causing agents generate different kinds of mutant p53, Athar notes. Whether CP-31398 can correct more than just damage due to UV light remains to be seen.
http://www.nature.com/news/2007/071203/full/news.2007.318.html |
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发表于 2007-12-10 12:11:57