What’s New in Melanoma Skin Cancer Research?
Causes, prevention, and early detection
Sunlight and ultraviolet (UV) radiation
Recent studies suggest there may be 2 main ways that UV exposure is linked to melanoma, but there is likely some overlap.
The first link is to sun exposure 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 damage the DNA in skin cells (melanocytes), which 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 thighs (in women) and trunk (in men), 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 might help either kind of melanoma to develop.
Researchers are studying if melanomas that develop from these types of UV exposure have different gene changes that might require them to be treated differently.
Most skin cancers can be prevented. The best way to lower the number of skin cancers 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’s important for health care professionals and skin cancer survivors to remind everyone about the dangers of too much UV exposure (both from the sun and from man-made sources such as tanning beds) and about how easy it can be to protect your skin from UV rays.
Melanoma can often be found early, when it is most likely to be 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. Many local American Cancer Society offices work 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.
Along with recommending staying in the shade, the American Cancer Society uses a slogan popularized in Australia as part of 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 genetic research
Scientists have made a great deal of progress in understanding how UV light damages DNA inside skin cells and how these changes can cause normal skin cells to become cancer cells.
Some people, though, inherit mutated (damaged) genes from their parents. For example, changes in the CDKN2A (p16) gene cause some melanomas that 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, limits, and downsides of testing for changes in this gene.
Some newer approaches to diagnosing skin cancer don’t require the removal of a skin sample. An example of such an “optical biopsy” is reflectance confocal microscopy (RCM). This technique allows the doctor to look at an abnormal area of skin to a certain depth without cutting into the skin.
RCM is used widely in Europe, and it’s now available in some centers in the US. It may be especially useful for people with many unusual moles, as it can cut down on the number of skin biopsies these people need. RCM might also be helpful in determining the edges of a melanoma, which could help during surgery.
This technique will likely become more widely available in the coming years.
Lab tests to help determine prognosis
Most melanomas found at an early stage can be cured with surgery. But a small portion of these cancers eventually spread to other parts of the body, where they can be hard to treat.
Recent research has shown that certain gene expression patterns in melanoma cells can help show if stage I or II melanomas are likely to spread. A lab test based on this research, known as DecisionDx-Melanoma, is now available. The test divides melanomas into 2 groups based on their gene patterns:
- Class 1 tumors have a low risk of spreading.
- Class 2 tumors have a higher risk of spreading.
This test might help tell if someone with early-stage melanoma should get additional treatment or if they need to be followed more closely after treatment to look for signs of recurrence.
While early-stage melanomas can often be cured with surgery, more advanced melanomas can be much harder to treat. But in recent years, newer types of immunotherapy and targeted therapies have shown a great deal of promise and have changed the treatment of this disease.
This type of treatment helps the body’s immune system attack melanoma cells more effectively. Some forms of immune therapy are already used to treat some melanomas (see Immunotherapy for Melanoma Skin Cancer).
Immune checkpoint inhibitors: Newer drugs such as pembrolizumab (Keytruda, nivolumab (Opdivo), and ipilimumab (Yervoy) block proteins that normally suppress the T-cell immune response against melanoma cells. These drugs have been shown to help some people with advanced melanomas live longer.
Researchers are now looking for ways to make these drugs work even better. One way to do this might be by combining them with other treatments, such as other types of immunotherapy or targeted drugs.
Researchers are also studying if these drugs can be helpful for earlier-stage melanomas. For example, they might prove to be useful before or after surgery for some melanomas to help lower the chance that the cancer will come back.
Newer immune checkpoint inhibitors with slightly different targets are now being studied as well.
Melanoma vaccines: Vaccines to treat melanoma are being studied in clinical trials.
These vaccines are, in some ways, like 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 can’t 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 used as a vaccine to try 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 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. The results of studies using vaccines to treat melanoma have been mixed so far, but many newer vaccines are now being studied and may hold more promise.
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), which are immune system cells taken from 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. This approach has looked promising in early studies, but it’s complex and is only being tested in a few centers.
Many studies are now looking to combine different types of immunotherapy, which may be more effective than any single treatment for advanced melanoma.
Targeted therapy drugs target parts of melanoma cells that make them different from normal cells. These 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 cells with BRAF gene changes: About half of all melanomas have changes in the BRAF gene, which helps the cells grow. Drugs that target the BRAF protein, such as vemurafenib (Zelboraf) and dabrafenib (Tafinlar), as well as drugs that target the related MEK proteins, such as trametinib (Mekinist) and cobimetinib (Cotellic), have been shown to shrink many of these tumors. These drugs are now often used to treat advanced melanomas that test positive for the BRAF gene change. Researchers are now looking at whether these drugs might be helpful before or after surgery for some earlier stage melanomas.
Other, similar drugs are now being studied as well.
One of the drawbacks of these drugs is that usually work for only a limited time before the cancer starts growing again. But studies have shown that combining a BRAF inhibitor with a MEK inhibitor results in longer response times, and some side effects (such as the development of other skin cancers) might actually be less common with the combination.
Drugs that target cells with changes in the C-KIT gene: A small number of melanomas have changes in the C-KIT gene. This is more likely in melanomas that start on the palms of the hands, soles of the feet, under the nails, or in certain other places.
Clinical trials are now testing drugs such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna), which are known to target cells with changes in C-KIT.
Drugs that target other gene or protein changes: Several drugs that target other abnormal genes or proteins are now being studied in clinical trials as well. Some examples include axitinib (Inlyta), pazopanib (Votrient), and everolimus (Afinitor).
Researchers are also looking at combining some of these targeted drugs with other types of treatments, such as chemotherapy or immunotherapy.
Last Medical Review: May 19, 2016 Last Revised: May 20, 2016