What’s New in Melanoma Skin Cancer Research?

Research into the causes, prevention, and treatment of melanoma is being done in medical centers throughout the world.

Causes, prevention, and early detection

Sunlight and ultraviolet (UV) radiation

Recent research suggests there may be 2 main ways that exposure to UV rays 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 (genes) in skin cells called 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 chronic sun exposure. This type of exposure may be the cause of many 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 different patterns of UV exposure have different gene changes that might require them to be treated differently.

Public education

Most melanomas (and other 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 people, especially parents, about risk factors and warning signs and symptoms. 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 contact 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 some of the DNA (gene) changes inside normal skin cells can lead them to become melanoma cells. In some cases, these gene changes can now be targeted with newer treatments for melanoma..

Some people inherit mutated (damaged) genes from their parents that raise their risk of melanoma. 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 might want to 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.

Diagnosis

Some newer approaches to diagnosing skin cancer don’t require the removal of a skin sample.

One type of “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.

Another technique now being studied is adhesive patch testing. Instead of cutting into the skin to get a biopsy sample, a sticky patch is placed over the suspicious area. When it’s removed it takes some of the top layers of skin with it, which can then be tested for certain gene changes that are often linked with melanoma. If one of these gene changes is found, a standard biopsy of the area can then be done. If no gene changes are found, a biopsy isn’t needed, and the area can be watched instead.

Lab tests to help determine prognosis (outlook)

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 main groups, based on their gene patterns:

• Class 1 tumors have a lower 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 a sentinel lymph node biopsy (SLNB) or additional treatment, or if they need to be followed more closely after treatment to look for signs of recurrence. Doctors are still studying the best of use of this test.

Tests of other genes and gene patterns are now being studied as well.

Treatment

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.

Immunotherapy

This type of treatment helps the body’s immune system attack melanoma cells more effectively. Some forms of immune therapy are now 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 are now one of the mainstays of treatment for advanced melanomas. 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, as an adjuvant (additional) treatment after surgery. Some have already been shown to be useful after surgery for melanomas that have reached the lymph nodes, where they can help lower the chance that the cancer will come back. Researchers are now studying if these drugs might be helpful for even earlier stage melanomas, or if they might be helpful if used before surgery (called neoadjuvant treatment) for some people.

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.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs): Some studies have shown that treating patients with tumor-infiltrating lymphocytes (TILs) can shrink melanoma tumors and possibly prolong life as well. TILs are immune system cells inside a tumor. Once a tumor is removed with surgery, the TILs can be separated out and then multiplied in the lab, after which they can be given back to the patient as an IV infusion. In studies done so far, patients are usually given chemotherapy before this treatment to help the body accept the TILs. After getting the TILs, patients might also be given an immunotherapy such as interleukin-2 (IL-2), which might help these immune cells better attack the cancer.

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.

Other immunotherapies: Other new forms of immunotherapy are also being studied. In addition, many studies are now looking at combining different types of immunotherapy, which may be more effective than any single treatment for advanced melanoma.

Targeted drugs

Targeted therapy drugs target parts of melanoma cells that make them different from normal cells. These drugs work differently from standard chemotherapy drugs. They work in some cases when chemotherapy doesn’t. They can also have different (and sometimes 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 or the related MEK proteins have been shown to shrink many of these tumors, especially when BRAF and MEK inhibitors are combined. 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.

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 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.