Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: SUNDAY, June 24, 1990 TAG: 9006210277
SECTION: EXTRA PAGE: E1 EDITION: METRO
SOURCE: NATALIE ANGIER THE NEW YORK TIMES
DATELINE: LENGTH: Long
They are racing to devise new therapies against malignant melanoma, the deadly skin cancer that is increasing faster than any other cancer in the world.
At several recent cancer meetings, epidemiologists and dermatologists presented stark new figures that they said make melanoma the most troublesome cancer they now confront.
They reported that the incidence of the skin malignancy has doubled since 1980, and that it continues to soar by 4 percent or 5 percent a year worldwide.
In that same period, they said, malignant melanoma climbed from being the third most common cancer among women between the ages of 25 and 29 to number one for the group, and the ninth most common cancer overall in the United States.
Last year, 27,300 people were diagnosed with melanoma, and 6,000 died of the disease.
"It's a near epidemic," said Dr. Darrell S. Rigel, a dermatologist and melanoma specialist at New York University Medical Center. "To have something double in 10 years is really amazing. No other cancer has this rate of increase."
Faced with these statistics, many researchers are working to design new therapies against the disease. When caught early enough, melanoma tumors, which resemble moles, can be surgically removed and the cancer completely cured. But once the malignancy has spread from the skin to other parts of the body, melanoma is among the most aggressive and lethal of cancers, resisting traditional methods of chemotherapy and radiation.
Researchers now believe that a far more promising approach to treating advanced melanoma is to coax the immune system to recognize melanoma cells as deadly and to destroy them.
Some investigators have crafted vaccines that spur the immune system to recognize melanoma cells and to produce antibodies and white blood cells to fight them.
Several of these vaccines are in or nearing large-scale clinical trials. Other investigators are employing powerful hormones like interferon and interleukin-2 to stimulate an immune response in patients.
"Two years ago I wouldn't have said that I have much hope for new treatments," said Dr. Alan N. Houghton, chief of the clinical immunology service at Memorial Sloan-Kettering Cancer Center in New York. "But now we have a whole set of new agents and new approaches that I think are going to make a difference in the future."
Still other scientists are striving to understand why melanoma defies many of the rules that apply to other cancers. They are scrutinizing the enzymes in the tumor cells to determine why melanoma can infiltrate more organs than almost any other type of malignancy.
They also are learning how stray melanoma cells that have broken away from the original tumor can lie dormant in the body for 10 years or longer before suddenly exploding into a deadly tumor mass at a distant site.
Scientists believe such insights will lead to dramatically improved cancer therapies.
"One absolutely critical, important point that we have learned by studying melanoma is that we can use a biological approach to alter a patient's immune system and cause cancer regression," said Dr. Steven A. Rosenberg, chief of surgery at the National Cancer Institute, part of the National Institutes of Health in Bethesda, Md.
But dermatologists stress that new treatments for advanced melanoma are still highly experimental. They say that the best treatment for the disease is to catch it at its earliest stages, when surgery can rout it out. Better still, say doctors, is to avoid excessive sun exposure and to wear a strong sun block while outdoors.
"The best thing to do about melanoma is not to get it," said Dr. Fred T. Valentine, an immunologist at New York University Medical Center. "That's the lesson folks still have to learn."
Melanoma is a cancer of the melanocytes, the cells that produce skin pigment. It is less common than basal cell carcinoma, a relatively benign type of skin tumor that usually appears on the face or hands and rarely spreads beyond the skin.
Some scientists blame part of the melanoma epidemic on the use of industrial and commercial chemicals that are thought to be depleting the ozone layer, the stratum of the upper atmosphere that blocks out many dangerous ultraviolet rays.
But the theory is hotly contested, and most researchers believe that a more important cause is the recent obsession with tanning.
They say that the steep rise in melanoma began when the bronzed "healthy" look replaced the porcelain complexion as a physical ideal, a trend that began on a wide scale in the '50s.
"It's insidious because there's a 20- to 30-year year lag period before the sun damage becomes clinically apparent," said Rigel. "What we're seeing now are the cancers that were initiated in the '60s and '70s, when people were outdoors more than they had been 20 years before, but when strong sunscreens were not yet widely available."
Buttressing the link between melanoma and recreational sunning are the locations on the body where the first tumors usually appear.
On men, melanoma tumors normally show up on the back, shoulders or belly, places that are usually exposed to strong sun only sporadically.
On women, melanomas most frequently occur on the legs, although they increasingly are appearing on the torso, probably a result, say researchers, of the popularity of two-piece bathing suits.
Wherever they crop up, the tumors usually are dark brown or black, slightly raised, with irregular edges.
Researchers say that the most dangerous type of exposure is binge sunning, which frequently results in bad burns. According to the American Cancer Society, people who have had three or more blistering sunburns before age 20 have five times the risk of getting melanoma of those who have never been sunburned.
But researchers say that the unusual danger of a bad sunburn does not mean that gradual or mild tanning is harmless. "There is no such thing as a safe suntan," said Rigel.
Other risk factors include a family history of the disease, a fair complexion and blond or red hair, and a noticeably freckled back and shoulders, indicating excessive sun exposure.
The highest rate of melanoma in the world is in Queensland, Australia, where many fair-skinned people of Irish and English extraction live beneath the scorching sub-equatorial sun. But blacks and Asians also develop melanoma, although at a much lower rate than do whites.
Researchers recently have determined the precise size of the tumor that can spell the difference between life and death, Rigel said. When the vertical thickness of the tumor is less than a 0.75 millimeters, or 1/32 of an inch, the removal of the tumor marks the end of the disease virtually 100 percent of the time. But if the tumor is thicker than an eighth of an inch - the width of a dime - it very likely already has metastasized, or spread.
Metastatic melanoma is one of the toughest of tumors to treat. For unknown reasons, it is invulnerable to most types of chemotherapeutic drugs that kill other cancer cells.
Radiation is sometimes used to treat melanoma, but the therapy can do little beyond shrinking tumors enough to relieve a patient's pain.
But scientists are optimistic that melanoma may be more amenable to new immune therapies than are other cancers. They have found that a melanoma cell has an unusually high number of antigens, or protruding proteins, on its surface, which could provide easy targets for the immune system to assault.
Researchers do not yet understand the function of the surface proteins, but they are exploiting them to design new therapies.
`'We believe that we can train the immune system to go out and destroy any melanoma that's been left behind after surgery," said Dr. Jean-Claude Bystra, director of the melanoma program at the New York University Kaplan Cancer Center.
Perhaps the most promising approach lies with a cancer vaccine, long a dream of oncologists. Researchers hope that by vaccinating a patient with telltale pieces of a cancer cell, they can spur the immune system to mount a fierce response against all cells in the body that bear those distinguishing marker proteins.
Furthest along is a melanoma vaccine developed by the team of Dr. Marc K. Wallack, chief of surgery at Mt. Sinai Medical Center in Miami Beach, Fla. They took a harmless version of the vaccinia virus, which causes smallpox, and infected melanoma cells with it in the laboratory.
They then pulverized the membranes of the infected melanoma cells, emerging with a combination of vaccinia particles and melanoma antigens. That mixture is injected into melanoma patients.
"The body knows how to react to viruses very well," said Wallack. "This vaccine calls attention to melanoma antigens, and therefore the immune system reacts to the melanoma proteins as well as to the viral proteins."
The researchers have found that, in responding to the virus-melanoma shot, the body generates a host of antibodies and white blood cells that recognize specific melanoma targets.
by CNB