Testing for and Treating Melanoma with the BRAF Mutation

BRAF genetic testing is used to identify mutations in the BRAF gene that can contribute to the development of melanoma. BRAF refers to the B-Raf proto-oncogene, the protein it makes is also known as a serine/threonine kinase. Oncogenes naturally turn on cell growth. But because of the mutation, oncogenes can cause normal cells to grow too fast and become cancerous.

The BRAF gene sends instructions to make a protein that transmits chemical signals as part of the pathway which controls several important cell functions. This pathway, called the RAS/MAPK pathway, influences the way cells2:

  1. Proliferate: grow and divide
  2. Differentiate: perform specific functions
  3. Migrate: move around
  4. Apoptose: programmed cell death

What is melanoma?

Melanoma is a skin cancer that starts in melanocytes, the body’s pigment-producing cells. It can be caused by UV radiation from the sun or other environmental causes. They can form harmless moles or become melanoma.

Melanomas often have mutations in the BRAF V600 gene. These changes affect the production of the BRAF protein and make cells grow faster.

Genetic testing for BRAF gene mutation

Genetic testing of melanoma is generally performed when the cancer is at stage 2C, stage 3 or stage 4. Doctors perform a tumor biopsy to test for the mutation. During the biopsy, tissue is removed from the tumor either by cutting, scraping or aspirating (use of a special needle to withdraw cells from the tumor).4 40-50% of all people with melanoma have the BRAF V600 mutation.3

Targeted therapy

Targeted therapy works differently than traditional chemotherapy.2 General chemotherapy attacks cancerous cells that divide quickly. There are other kinds of drugs that can target specific parts of cells that block tumor cell growth rather than just attacking all cells. The presence of the genetic mutation can guide physician decisions about selecting appropriate treatment.3

When someone has the BRAF mutation they may need targeted therapy, treatment with specific cancer drugs that can shrink or slow the growth of tumors. However, targeted medicines are not as effective, and sometimes dangerous to people who don't have the mutation.4

BRAF inhibitors

Drugs that target the BRAF protein are called BRAF inhibitors. There is an MEK gene that works in concert with the BRAF gene. MEK inhibitors attack MEK proteins. People with the BRAF mutation will likely be treated with both a BRAF inhibitor and a MEK inhibitor, as this combination generally works better than either drug alone. The combination of medications can benefit some patients, helping them to survive longer by shrinking tumors. The drugs may not be as effective used alone and can be dangerous to people without the mutation. Some people experience fewer side effects when the drugs are combined.

Medication options

Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) are drugs that target the BRAF protein. They come in pill or capsule form and are taken one or two times a day as prescribed. According to the prescribing information, common side effects include thickening skin, rash, itching, sun sensitivity, headache, fever, joint pain, fatigue, hair loss, and nausea. More serious side effects can include problems with heart rhythm, the liver, kidney failure, severe allergic reactions, skin or eye problems, bleeding, and increased blood sugar level.

MEK inhibitor pills include trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi). Administered once or twice a day, some people experience side effects including rash, nausea, diarrhea, swelling, and sensitivity to sunlight. Uncommon serious side effects can include damage to the heart, lung, or liver; bleeding or blood clots; vision problems; muscle damage; and skin infections.

Side effects

Some of these medications can cause new squamous cell skin cancers to grow. Generally, less serious than melanoma, if presenting they should be removed by your doctor. Skin checks are carried out during treatment and beyond. Any new growths or abnormal skin changes should be reported.

Find out what's right for you

Ask your doctor or dermatologist if you have been tested for the BRAF gene. This might change the way that you are treated. Many targeted therapies and even immunotherapies are available to treat metastatic melanomas, so there are options for you.

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