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The Honolulu Advertiser
Posted on: Tuesday, August 7, 2001

Cream may prevent skin cancer

Associated Press

The key to preventing skin cancer is protecting yourself from the sun, but too few people heed that advice: Skin cancer strikes more than 1 million Americans annually and is on the rise.

Now researchers have developed an experimental cream that may repair some sun damage and help ward off cancer. Consider it gene therapy in a bottle, a lotion containing an enzyme that repairs sun-damaged DNA.

It reduced the incidence of the most common form of skin cancer when tested on some of the world's most sun-sensitive people — sufferers of a rare inherited disease called xeroderma pigmentosum, or XP, who can blister in minutes and suffer skin cancer at 1,000 times the rate of average people.

Might the cream, called Dimericine, also help the general population? Ultraviolet rays damage DNA the same way in XP patients as in anyone else. So this fall, researchers plan to take Dimericine to three sunny cities — San Diego, Los Angeles and Jacksonville, Fla. — to test it on 600 people who have had one skin cancer removed and thus are at high risk for more.

Don't put away your sunscreen yet. Even if the cream ultimately works, it's not perfect and so wouldn't be a license to fry.

But, "right now when someone forgets or misuses or washes off a sunscreen and has a sunburn, there's nothing that can be done for the long-term damage that's been done to the skin," says molecular biologist Daniel Yarosh, who created Dimericine.

Now that scientists have pinpointed UV-caused gene mutations, "sooner or later, there's going to be a morning-after cream" to help fix them, adds Yale University dermatologist Dr. David Leffell.

Some 1.3 million Americans will be diagnosed with basal or squamous cell carcinoma this year, the most common skin cancers and the ones easily cut away if caught early, according to the American Cancer Society. Thousands more, like President Bush, will have removed sun-induced lesions called actinic keratoses that can turn into squamous cell cancer.

The deadliest skin cancer, melanoma, will strike an additional 51,000 Americans, a toll rising 3 percent a year. Skin cancer will kill almost 10,000 this year, the majority melanoma sufferers.

The best protection is to limit sun exposure beginning in childhood, dermatologists say. Sunburns early in life are considered the most dangerous; doctors even have begun seeing melanoma in 20-somethings.

Slip on a shirt, slop on sunscreen and slap on a hat anytime you're in the sun, but especially between 10 a.m. and 4 p.m. when UV rays are strongest, says the cancer society's new "slip, slop, slap" sun-safety campaign.

One burn doesn't mean cancer. Skin has complex repair mechanisms that remove about half of UV-damaged DNA in 24 hours, half the remaining damage in another day, and so on, Yarosh explains. But over time, missed repairs build up. Enough built-up damage equals cancer.

A bacterial enzyme called "T4 endonuclease V" has long been known to help repair DNA. But no one knew how to get it through skin. Then Yarosh's biotechnology company, AGI Dermatics, put the enzyme into microscopic fat bubbles called liposomes that can slip inside skin cells. There, the enzyme binds to UV-caused DNA mutations and initiates repair.

First tested were XP patients, who have an incurable gene defect that leaves them unable to repair most UV damage. Thirty applied either Dimericine or a dummy lotion to their face and hands daily for a year. Dimericine users had a 30 percent reduction in basal cell carcinoma, and a dramatic 68 percent reduction in precancerous actinic keratoses.

Because the drug doesn't seem to penetrate below the epidermis, the skin's upper layer, so far no one has experienced side effects, Yarosh reported in The Lancet medical journal.

He is preparing to seek Food and Drug Administration approval of Dimericine for XP suffers. Next come studies to see if it could help protect against general skin cancer, too.

Dimericine may be "a very important step forward," says Dr. Martin Weinstock, chairman of the cancer society's skin cancer advisory board. But for now, avoiding the sun is a proven, easy preventive, he stressed. "People need to slip, slop, slap."