Research into the causes, prevention, and treatment of melanoma is under way in many medical centers throughout the world.

Causes and prevention

Sunlight and UV radiation

Recent studies suggest there may be 2 general ways that UV exposure contributes to melanoma, (although there is likely some overlap between these).

The first is exposure to sunlight as a child and teenager. People with melanoma often have an early history of sunburns, although this isn't necessary. This early sun exposure starts a change in skin cells (melanocytes) that may eventually turn into melanoma. Doctors who propose this think that this might help explain melanomas that occur on the legs and trunk -- areas that generally aren't exposed to the sun as much in adulthood.

The second kind of melanoma occurs on the arms, neck, and face. These areas are chronically exposed to sun, particularly in men. Tanning booths may also encourage these kinds of melanomas to develop.

Public education

Most skin cancer is preventable. The greatest reduction in the number of skin cancer cases and a reduction in the pain and loss of life from this disease will come from prevention and early detection strategies. This involves educating the public, especially parents, about skin cancer risk factors. It is important for health care professionals and skin cancer survivors to remind everyone about the dangers of excessive sun exposure 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 detecting melanoma 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 locally 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.

A slogan popularized in Australia is now used as the American Cancer Society's skin cancer prevention message in the United States. "Slip! Slop! Slap! ... and Wrap" is a catchy way of remembering to slip on a shirt, slop on sunscreen, slap on a hat, and wrap on sunglasses when outdoors 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.

They have also found that DNA damage affecting certain genes is important in causing melanocytes to change into a melanoma. Often this damage is due to sun exposure.

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 benefits, limitations, and potential disadvantages 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, ribonucleic acid, or 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 sensitive and 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 more sensitive than routine microscopic testing in 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 false positive results (where the test is positive even though there is no cancer in the sample), which might lead them to advise unnecessary treatment for some patients. That's why this test is not currently recommended. Research studies are now in progress to learn more about how results should influence choice of treatment.

Treatment

Immune therapy

This approach to melanoma treatment includes several strategies for helping the body's immune system attack melanoma cells more effectively. Some forms of immune therapy, such as 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.

Experimental melanoma vaccines help "train" a person's immune system to fight melanoma in a more specific way. As researchers learn more about how the immune system works, these immune treatments should become more effective. This is a major area of current research, although melanoma vaccines are only available in clinical trials at this time.

Other forms of immunotherapy are also being studied. A recent small study showed that treating patients with tumor-infiltrating lymphocytes (TILs), immune system cells found in tumors, could shrink melanoma tumors and possibly prolong life as well. Another study found that T cells (a type of white blood cell) that had their genes altered in the lab could cause tumors to shrink in a small fraction of patients. Further studies of these new treatments are now under way.

Molecular targeting

As doctors have discovered some of the gene abnormalities in melanoma cells, they have begun to develop drugs to attack these abnormalities.

An example is a gene called BRAF, which is abnormal in most melanoma cells. Several drugs that target the activity of this gene are being developed and studied.

Another target is CTLA-4, a protein that normally suppresses the T-cell immune response, which might help melanoma cells to survive. Drugs that counteract CTLA-4, such as ipilimumab, are now in late stage clinical trials. They may prove to be most effective when combined with other treatments such as immunotherapy or chemotherapy.

About one third of certain types of melanomas have changes in a gene called c-kit. 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

Some drugs that are already used to treat other cancers, such as imatinib (Gleevec), are known to target cells with changes in c-kit. Clinical trials are now under way to see if imatinib and similar drugs might help people with these types of melanoma.

Several drugs that target other abnormal genes or proteins are now being studied in clinical trials as well.

Gene therapy

A promising new approach to treating melanoma adds certain genes to the cancer cells. Gene therapy can be used to try to replace some of the damaged genes in melanoma cells, to add a gene that can block to melanoma cells' ability to make certain proteins, or to help boost the immune response against them. Many researchers feel that progress in this third strategy is the farthest along. Clinical trials testing these gene therapy approaches are currently in progress.

Last Medical Review: 06/05/2008
Last Revised: 05/14/2009