Photos by Roger Camp
A Killer Tan
While genetics may be a factor in many skin cancers, a primary culprit is exposure to the sun.
by Jon NalickAt first, computer specialist John Gertwagen was not worried about the mole growing larger on his left shoulder. After all, the physicians who examined it in early 1995 said it was probably nothing to worry about.
But the dark red mole kept growing until it was a half-inch across. By the time a lab test in September of that year showed there was something seriously wrong, it was too late. The tumor was diagnosed as a malignant melanoma, one of the deadliest forms of cancer, and it had already begun to spread.
"My HMO oncologist said that there was no established treatment for it and that my prognosis was not very good. I had maybe two years to live," says Gertwagen, 50, of Thousand Oaks.
For the next 12 months, he would undergo surgeries, radiation treatments and interferon injections, but with many unpleasant side effects and only limited success.
Finally, in a last ditch effort to fight the disease, Gertwagen enrolled in a experimental clinical trial at the USC/Norris Comprehensive Cancer Center and Hospital that ultimately eradicated all traces of the melanoma from his body.
"I'm now three years into my two-year life span," he says. "I like beating the odds."
Gertwagen is one of almost 42,000 Americans each year who are diagnosed with malignant melanoma, an extremely dangerous form of cancer that originates in the cells that produce skin pigmentation and routinely spreads to other parts of the body. Melanomas account for only four percent of all skin cancer cases, but about 80 percent of skin cancer deaths. More than 7,300 people in the U.S. are expected to die of the illness this year alone.
Further, American Cancer Society statistics show that half of all Americans who live to age 65 are likely to have skin cancer at least once.
Ninety-six percent of those cases will be non-melanoma cancers such as basal or squamous cell carcinomas-cancers that affect the middle and lowest layers of the skin, grow slowly and rarely spread. As a result, they are nearly 100 percent curable when diagnosed at an early stage.
At the USC/Norris, researchers are seeking new ways of preventing and fighting skin cancers using powerful new drugs, gene therapies and community education.
Jeffrey S. Weber, M.D., Ph.D., associate professor of medicine and director of immunotherapy at the USC/Norris, says prevention and education are the crucial first steps in combating the disease.
"Everyone should be aware of the 'ABCDs,'" he says, referring to the guidelines that help identify suspicious moles or skin growths that could signal melanoma. "Once melanomas are allowed to grow past the skin, relapse and possibility of death becomes almost inevitable. That's why you need to know what to look for."
'ABCD' stands for:
o Asymmetry-one half of the mole does not match the other;
o Borders-growths with shaggy or indistinct edges;
o Color-the color over the mole is not the same. There may be differing shades of tan, brown, or black, and sometimes patches of red, blue, or white;
o Diameter-growths that are larger than a pencil eraser, or about six millimeters.
"If you have a mole that meets two or more of those criteria, that's the kind of lesion that should make you think about seeing a dermatologist for a biopsy," Weber says.
The most important sign of melanoma is a change in size, shape, or color of a mole. Some melanomas do not fit the ABCD rule described above, so it is particularly important to be aware of changes in skin lesions.
Non-melanoma skin cancers vary widely in appearance, from small waxy or red lumps, to rough, dry or scaly patches, or lumps that bleed or develop a crust. Such changes in skin do not necessarily signify skin cancer, but any symptoms that last longer than two weeks should be checked by a physician.
Education of the public is crucial because "heightened awareness clearly leads to early detection and probably will help prolong survival, especially in patients with melanoma," Weber says.
Melanoma strikes about 35 people out of every 100,000 each year-mostly light-skinned people, those who sunburn easily, people with blue-green eyes or red hair.
"That doesn't sound like a lot, but multiply your annual risk by 50 to 60 years and you get a 1.5 percent risk of melanoma in your lifetime," he says.
Weber notes that while genetics can be a factor in many skin cancers, the primary culprit is often exposure to the sun.
Solar radiation, especially in the ultraviolet wavelengths, can scramble the genetic information carried within its cells. That damage can promote the growth of cancers by triggering runaway cellular division or by hampering the body's natural ability to stop such growth, he says.
Weber says the best way to help prevent skin cancer is to avoid exposure to the sun, especially during the peak hours between 10 a.m. and 3 p.m., and to wear sunglasses and wide-brimmed hats when going outside during the day.
In addition, everyone-particularly those with fair skin or who sunburn easily-should wear sunscreens with a SPF factor of 15 or higher on areas exposed to the sun. Sunscreens should also be used on hazy days or days with light or broken cloud cover because the UV light still comes through, he says.
Further, sunscreens must be applied before sun exposure to be effective and should be used on all sun-exposed skin. Many sunscreens will wear off with sweating and swimming and must be reapplied for maximum effectiveness.
Weber dismissed recent studies that suggest a correlation between sunscreen use and an increased incidence of skin cancer, saying the studies were almost certainly reflecting a higher incidence of sun exposure among sunscreen users.
Emphasizing that point, he warns that "enough exposure to the sun will negate the effects of sunscreen, so wearing sunscreen is not a guarantee that you won't get cancer."
Recent studies that link sun exposure to a reduced risk of breast cancer must not be construed as a prescription to spend more time in the sun. While exposure to the sun does cause the body to manufacture vitamin D-a potential deterrent to breast cancer-the tradeoff comes in increased skin cancer risk, premature aging of the skin and wrinkles. Besides, vitamin D can be obtained through a healthful diet that includes fish oil, fatty fish, egg yolk and liver. Milk and some cereals are also fortified with vitamin D.
Aside from educating the public, USC/Norris researchers are taking other approaches to preventing cancers.
For example, Jane Fountain, Ph.D., assistant professor of biochemistry and molecular biology, investigates the genes responsible for fighting and promoting cancers.
"We're working at the DNA level, what I call the 'basement level,' of the disease to look for the alterations and combinations of alterations in genes that give rise to melanomas," she says.
Doing that, she says, will provide a genetic blueprint for melanoma progression-showing how and when genes mutate during melanoma evolution. This will eventually allow for the development of better treatments for melanoma and better methods for diagnosing the disease.
One interesting area of study is the role that the p16 gene on chromosome 9 may play in the occurrence of melanoma. The gene acts as a tumor suppressor in the body, inhibiting the growth of cancers. When a person inherits a faulty copy of the gene, or when something in the environment damages it, melanomas and other cancers can evolve.
Fountain cautions that the gene is only one of many sites that may play a role in melanoma development and that it often takes many years to unravel the full puzzle of cancer progression.
"We're really still at the nuts and bolts stage. p16 is the first gene that really appears to play a dominant role. It's probably a target for mutation very early on in disease so it's an initiating event," she says.
Fountain also investigates the roles that genes on chromosomes 6 and 11 play in the intermediate stages of cancer progression.
"We think that on either or both of chromosomes there may be genes that inhibit metastasis," the process wherein cancers advance to other parts of the body, she says.
Fountain says that once the genes and their functions have been established, then the door is open for providing gene therapies, where the functions of a mutated gene can be replaced. Another alternative would be to use drugs to manipulate biochemical pathways, so the consequences of losing a particular gene are alleviated and the cancer cell growth becomes arrested.
Until prevention strategies are perfected, Fountain says people must take responsibility for examining their bodies regularly for skin cancers so they can be treated in time.
Physicians generally treat non-melanoma skin cancers with minor surgery, radiation treatments, topical medicines, oral chemotherapy or freeze off the tumor with liquid nitrogen. Malignant melanoma treatments are usually more involved because of the aggressive and devastating nature of the disease-for which no standard treatment yet exists.
Weber's team is now testing several chemotherapies and other new treatments that show promise in combating melanoma. The treatments include the use of therapeutic agents, called adjuvants, to boost the immune system's response, and melanoma vaccines that use snippets of protein called peptides to increase the body's chances of mounting a response to a tumor.
Because cancer cells are not foreign invaders like viruses or bacteria, the immune system often has a hard time perceiving them as dangerous, much like a soldier cannot recognize an enemy in battle who wears the same uniform. Melanoma vaccines essentially teach the body how to recognize cancerous cells as the enemy and stimulate the immune system to launch a devastating counterattack using its own T-cells.
Taking another approach to fighting cancers, Weber's team is also investigating a new compound called DAC that is designed to reactivate a p16 gene that has become dormant in a melanoma cell. In some cases, the gene becomes inactivated when it undergoes a process called "methylation," and Weber hopes that DAC can repair this damage and restore the gene's tumor-fighting abilities.
Weber says that while clinical trials are experimental and have no guarantee of success, they often provide the only realistic hope of survival for people with advanced metastatic cancers.
"For many cancers there simply is no known effective standard therapy and patients should go into clinical trials," Weber says.
Cancer patient John Gertwagen, whose treatment with the melanoma vaccine removed all traces of the disease, says he agrees, adding that without the treatment he received at the USC/Norris, he would probably not be alive today.
"The biggest message I have for people is to be active in seeking treatment. When I was diagnosed, I didn't start a deathwatch. I committed myself to do everything I could to beat the problem," he says.
Gertwagen praises the USC/Norris program for the success of his treatment, and especially Weber's contributions.
"I have in one way or another interacted with six M.D.s in the process of getting my cancer treated and Dr. Weber is head and shoulders above the rest. Some of the physicians I've met have been excellent technicians and some have been excellent caregivers, but he is both," Gertwagen says.
"I've been incredibly pleased with every day of the last year. It's like a new lease on life."
