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Targeted 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.

Targeted drugs can be very helpful in treating advanced melanomas when the cancer cells have certain gene changes.

If you have melanoma that has spread beyond where it started, a biopsy sample of it will likely be tested to see if the cancer cells have one of these gene changes. This is known as biomarker testing.

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.

Drugs that target the BRAF protein (BRAF inhibitors) or the related MEK proteins (MEK inhibitors) can often be helpful in treating these melanomas, although they aren’t likely to work on melanomas that 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 that target the BRAF protein directly.

These drugs can often be helpful for people whose melanoma has spread or can’t be removed completely.

Dabrafenib can also be used (along with the MEK inhibitor 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, typically 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 can be used to treat melanoma that has spread or can’t be removed completely.

Trametinib can also be used along with dabrafenib after surgery in people with stage III melanoma, where it can help lower the risk of the cancer coming back.

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

MEK inhibitors 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.

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, throat, genital, or anal area (known as mucosal melanomas)
• 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 an advanced 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 will be helpful.

Drugs that target cells with other gene changes

Some melanomas might have changes in other genes that can be targeted with certain drugs. For example, tests might be done on the melanoma cells to look for changes in genes such as NRAS, ALK, ROS1, and the NTRK genes. These gene changes aren’t common in melanomas, but some targeted drugs might be a treatment option if a change in one of these genes is found.

Drugs that target other gene changes are also being studied in clinical trials.