Targeted therapy for melanoma skin cancer
As doctors have found some of the gene changes that make melanoma cells different from normal cells, they have begun to develop drugs that attack these changes. These 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. These changes cause the gene to make an altered BRAF protein that signals the melanoma cells to grow and divide quickly. Some drugs target this and related proteins.
If you have advanced melanoma, a biopsy sample of it might be tested to see if the cells contain a BRAF mutation. Drugs that target the BRAF protein (or the MEK proteins) are not likely to work in patients whose melanomas have a normal BRAF gene.
Vemurafenib (Zelboraf) and dabrafenib (Tafinlar) are drugs attack the BRAF protein directly.
These drugs shrink tumors in about half of the people whose metastatic melanoma has a BRAF gene change. They can also prolong the time before the tumors start growing again and help some patients live longer, although the melanoma typically starts growing again eventually.
These drugs are taken as pills or capsules, twice a day. Common side effects can include skin thickening, headache, fever, joint pain, fatigue, hair loss, rash, itching, sensitivity to the sun, 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, and increased blood sugar levels.
Some people treated with these drugs develop new skin cancers called squamous cell carcinomas. 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.
The MEK gene is in the same signaling pathway inside cells as the BRAF gene, so drugs that block MEK proteins can also help treat melanomas with BRAF gene changes.
The MEK inhibitors trametinib (Mekinist) and cobimetinib (Cotellic) have been shown to shrink some melanomas with BRAF changes. They are pills taken once a day. Common side effects can include rash, nausea, diarrhea, swelling, and sensitivity to sunlight. Rare but serious side effects can include heart damage, excess bleeding, loss of vision, lung problems, and skin infections.
When used by themselves, these drugs don’t seem to shrink as many melanomas as the BRAF inhibitors. A more 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 a gene called C-KIT that help them grow. These gene 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 research and treatment of melanoma of the skin?”).
Last Medical Review: 03/19/2015
Last Revised: 02/01/2016