Targeted Therapy for Melanoma Skin Cancer

These drugs target parts of melanoma cells that make them different from normal cells. Targeted drugs work differently from standard chemotherapy drugs, which basically attack any quickly dividing cells. Sometimes, targeted drugs work when chemotherapy doesn’t. They can also have less severe side effects. Doctors are still learning the best way to use these drugs to treat melanoma.

Drugs that target cells with BRAF gene changes

About half of all melanomas have changes (mutations) in the BRAF gene. Melanoma cells with these changes make an altered BRAF protein that helps them grow. Some drugs target this and related proteins, such as the MEK proteins.

If you have melanoma, a biopsy sample of it might be tested to see if the cancer cells have a BRAF mutation. Drugs that target the BRAF protein (BRAF inhibitors) or the MEK proteins (MEK inhibitors) aren’t likely to work in people whose melanomas have a normal BRAF gene.

Most often, if a person has a BRAF mutation and needs targeted therapy, they will get both a BRAF inhibitor and a MEK inhibitor, as combining these drugs often works better than either one alone.

BRAF inhibitors

Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) are drugs attack the BRAF protein directly.

These drugs shrink or slow the growth of tumors in some people whose metastatic melanoma has a BRAF gene change. They can also help some patients live longer, although the melanoma typically starts growing again eventually.

Dabrafenib can also be used (along with trametinib; see below) after surgery in people with stage III melanoma, where it can help lower the risk of the cancer coming back.

These drugs are taken as pills or capsules, once or twice a day. Common side effects can include skin thickening, rash, itching, sensitivity to the sun, headache, fever, joint pain, fatigue, hair loss, and nausea. Less common but serious side effects can include heart rhythm problems, liver problems, kidney failure, severe allergic reactions, severe skin or eye problems, bleeding, and increased blood sugar levels.

Some people treated with these drugs develop new squamous cell skin cancers. These cancers are usually less serious than melanoma and can be treated by removing them. Still, your doctor will want to check your skin often during treatment and for several months afterward. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.

MEK inhibitors

The MEK gene works together with the BRAF gene, so drugs that block MEK proteins can also help treat melanomas with BRAF gene changes. MEK inhibitors include trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi).

These drugs are pills taken once or twice a day. Common side effects can include rash, nausea, diarrhea, swelling, and sensitivity to sunlight. Rare but serious side effects can include heart lung, or liver damage; bleeding or blood clots; vision problems; muscle damage; and skin infections.

Again, the most common approach is to combine a MEK inhibitor with a BRAF inhibitor. This seems to shrink tumors for longer periods of time than using either type of drug alone. Some side effects (such as the development of other skin cancers) are actually less common with the combination.

Drugs that target cells with C-KIT gene changes

A small portion of melanomas have changes in the C-KIT gene that help them grow. These changes are more common in melanomas that start in certain parts of the body:

  • On the palms of the hands, soles of the feet, or under the nails (known as acral melanomas)
  • Inside the mouth or other mucosal (wet) areas
  • In areas that get chronic sun exposure

Some targeted drugs, such as imatinib (Gleevec) and nilotinib (Tasigna), can affect cells with changes in C-KIT. If you have a melanoma that started in one of these places, your doctor may test your melanoma cells for changes in the C-KIT gene, which might mean that one of these drugs could be helpful.

Drugs that target different gene changes are also being studied in clinical trials (see What’s new in melanoma skin cancer research?).

The American Cancer Society medical and editorial content team

Last Medical Review: May 19, 2016 Last Revised: June 28, 2018
