Research into the causes, prevention, and treatment of melanoma is under way in many medical centers throughout the world.
Causes, prevention, and early detection
Sunlight and ultraviolet (UV) radiation
Recent studies suggest there may be 2 general ways that UV exposure is linked to melanoma, but there is likely some overlap.
The first link is to sun exposure to as a child and teenager. People with melanoma often have an early history of sunburns or other intense sun exposures, although not everyone does. This early sun exposure may cause changes in skin cells (melanocytes) that starts them on a path to becoming melanoma cells many years later. Some doctors think this might help explain why melanomas often occur on the legs and trunk – areas that generally aren't exposed to the sun as much in adulthood.
The second link is to melanomas that occur on the arms, neck, and face. These areas are chronically exposed to sun, particularly in men. Tanning booths may encourage either kind of melanoma to develop.
Public education
Most skin cancer can be prevented. The best way to reduce the number of skin cancer cases and the pain and loss of life from this disease is to educate the public, especially parents, about skin cancer risk factors and warning signs. It is important for health care professionals and skin cancer survivors to remind everyone about the dangers of excess UV exposure (from the sun and from man-made sources such as tanning beds) and about how easy it can be to protect your skin against too much UV radiation.
Melanoma should be detected early, when it is most likely to be completely cured. Monthly skin self-exams and awareness of the warning signs of melanomas may be helpful in finding most melanomas when they are at an early, curable stage.
The American Academy of Dermatology (AAD) sponsors annual free skin cancer screenings throughout the country. The American Cancer Society works closely with the AAD to provide volunteers for registration, coordination, and education efforts related to these free screenings. Look for information in your area about these screenings or call the American Academy of Dermatology for more information. Their telephone number and Web site are listed in the "Additional resources" section.
The American Cancer Society uses a slogan popularized in Australia as its skin cancer prevention message in the United States. "Slip! Slop! Slap! ... and Wrap" is a catchy way to remember when going outdoors to slip on a shirt, slop on sunscreen, slap on a hat, and wrap on sunglasses to protect your eyes and the sensitive skin around them.
Melanoma DNA research
Scientists have made a great deal of progress during the past few years in understanding how UV light damages DNA and how changes in DNA cause normal skin cells to become cancerous.
On the other hand, some people may inherit mutated (damaged) genes from their parents. For example, changes in the CDKN2A (p16) gene cause some melanomas to run in certain families. People who have a strong family history of melanoma should speak with a cancer genetic counselor or a doctor experienced in cancer genetics to discuss the possible benefits, limitations, and downsides of testing for changes in this gene.
Molecular staging
Advances in melanoma DNA research are also being applied to molecular staging. In ordinary staging, a lymph node removed from a patient is looked at under a microscope to see if melanoma cells have spread to the lymph node.
In molecular staging, RNA (a chemical related to DNA), is extracted from cells in the lymph node. Certain types of RNA are made by melanoma cells but not by normal lymph node cells. A sophisticated test called reverse transcription polymerase chain reaction (RT-PCR) is used to detect these types of RNA.
Early studies have found that RT-PCR is better than routine microscopic testing at detecting the spread of melanoma to lymph nodes. This test may eventually help identify some patients who might benefit from additional treatment such as immunotherapy after surgery. However, some doctors are concerned that this test may lead to unnecessary treatment for some patients, which is why this test is not currently recommended. Studies are now in progress to learn more about how results should influence choice of treatment.
Treatment
Immunotherapy
This type of melanoma treatment includes several approaches for helping the body's immune system attack melanoma cells more effectively. Some forms of immune therapy, such as ipilimumab (Yervoy), cytokines (interferon-alpha and interleukin-2), and the BCG vaccine are already used to treat some melanomas. They work by boosting the immune system in a general way.
Ipilimumab targets CTLA-4, a protein that normally suppresses the T-cell immune response, which might help melanoma cells to survive. This drug has been shown to help some people with advanced melanomas live longer. Researchers are now trying to determine if it might be useful earlier in the course of the disease. Other drugs that counteract CTLA-4 are now being studied as well.
Melanoma vaccines
Vaccines directed at melanoma are being studied in clinical trials. They are experimental therapies that do not yet have proven benefit.
These vaccines are, in some ways, similar to the vaccines used to prevent diseases such as polio, measles, and mumps that are caused by viruses. Such vaccines usually contain weakened viruses or parts of a virus that cannot cause the disease. The vaccine stimulates the body's immune system to destroy the more harmful type of virus.
In the same way, killed melanoma cells or parts of cells (antigens) can be injected into a patient as a vaccine in an attempt to stimulate the body's immune system to destroy other melanoma cells in the body. Usually, the cells or antigens are mixed with other substances that help boost the body's immune system as a whole. But unlike vaccines that are meant to prevent infections, these vaccines are meant to treat an existing disease.
Making an effective vaccine against melanoma has proven to be harder than making a vaccine to fight a virus. Clinical trials are testing the value of treating advanced melanoma patients with vaccines, sometimes combined with cytokine therapy as well. The results of these studies have been mixed so far, but newer vaccines may hold more promise.
In a recent clinical trial of patients with advanced melanoma, adding a vaccine to high-dose interleukin-2 (IL-2) increased the portion of tumors that shrank and the length of time before they started growing again better than just giving IL-2 alone. But it's not yet clear if this vaccine can help people live longer.
Other immunotherapies
Other forms of immunotherapy are also being studied. Some early studies have shown that treating patients with high doses of chemotherapy and radiation therapy and then giving them tumor-infiltrating lymphocytes (TILs), immune system cells found in tumors, can shrink melanoma tumors and possibly prolong life as well. Newer studies are looking at changing certain genes in the TILs before they are given to see if this can make them more effective at fighting the cancer. Further studies of these new treatments are now under way.
Targeted drugs
As doctors have discovered some of the gene changes in melanoma cells, they have begun to develop drugs that attack these changes. These targeted drugs work differently from standard chemotherapy drugs. They may work in some cases when chemotherapy doesn't. They may also have less severe side effects.
Drugs that target changes in the BRAF gene
About half of all melanomas have changes in a gene called BRAF. A drug called vemurafenib (PLX4032) has shown promising results in early studies, significantly shrinking tumors in more than half of people whose metastatic melanoma has a BRAF gene change. The drug does not appear to cure these cancers, but it seems to delay the time before they start growing again. It is not yet clear if this drug can help people live longer, but further studies are under way. If these studies continue to show the drug is effective, doctors may soon start testing melanoma samples in patients to see if they contain the BRAF gene, in which case this drug may be used.
Other drugs that target BRAF gene changes are now being developed and studied as well.
Drugs that target changes in the c-kit gene
Certain types of melanomas often have unusual gene changes. This often includes melanomas that start in certain areas:
- On the palms of the hands, soles of the feet, or under fingernails
- Inside the mouth or in other mucosal areas
- In areas that get chronic sun exposure
About one third of these uncommon melanomas have changes in a gene called c-kit. Some drugs that are already used to treat other cancers, such as imatinib (Gleevec) and nilotinib (Tasigna), are known to target cells with changes in c-kit. Clinical trials are now under way to see if these and other drugs might help people with these types of melanoma.
Drugs that target other gene or protein changes
Several drugs that target other abnormal genes or proteins, such as sorafenib (Nexavar), bevacizumab (Avastin), temsirolimus (Torisel), and everolimus (Afinitor), are now being studied in clinical trials as well.
Researchers are also looking at combining some of these targeted drugs with other types of treatments, such as chemotherapy or immunotherapy.
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