This page was reviewed under our medical and editorial policy by
Herbert L. Duvivier, MD, JD, Hematologist and Medical Oncologist
This page was updated on February 24, 2023.
While chemotherapy attacks quickly dividing cells, whether they’re healthy or cancerous, targeted drugs instead attack parts of cells that differentiate them from normal cells, and that cause uncontrolled cell growth (cancer). These targeted drugs (inhibitors) appear to be helpful in treating advanced skin cancer that has changes in certain genes.
One that seems to play a role in skin cancer is the BRAF gene. About half of patients with metastatic melanoma have the BRAF mutation, according to the American Society of Clinical Oncology Educational Book.
The BRAF gene provides the blueprint for a protein (an oncogene) that plays a role in cell growth. In healthy people, the oncogene turns on and off as needed. In those who have a BRAF mutation, the switch is stuck in the on position, and the gene keeps telling cells to grow. Cancer happens when new cells keep growing and old cells don’t die.
There are a number of different BRAF mutations. The most common is V600E.
Another gene that has been implicated is the MEK gene. This gene works with the BRAF gene to provide instructions for making MEK1, a protein kinase that helps control proper cell growth and division.
Inhibitors have been developed that target the BRAF and MEK genes.
If you have a melanoma, your doctor will want to know whether you have a BRAF mutation and will likely order a BRAF genetic test.
The test requires your health-care provider to obtain a small piece of your tumor and send it to a molecular laboratory for evaluation. If the tumor is on your skin, your doctor is likely to cut or scrape it to take a small piece. If it’s deep inside your body, the doctor will use a special needle.
Sometimes, melanoma cells are removed during surgery and sent to the lab for genetic testing.
If the lab sees mutations in your BRAF gene, your melanoma will be described as BRAF positive.
You don’t need to do anything to prepare for this test. The test may cause slight-but-brief discomfort at the site where the sample was taken.
Drug therapies that attack the BRAF protein directly and are approved by the U.S. Food and Drug Administration (FDA) are:
These drugs are available as pills, to be taken once or twice daily. It’s important to follow directions and take them exactly as prescribed.
If you vomit after taking your pill, don’t take another. Wait until your next dose. Don’t double-dose to replace a missed one.
Possible side effects include:
More serious side effects include:
You may be told to stop taking your medication—temporarily or permanently—if you can’t tolerate the side effects.
Some patients on BRAF inhibitors may develop squamous cell skin cancer. This type of skin cancer is considered less serious than melanoma and is typically treated with surgery. If you notice new growths or abnormal areas on your skin while on BRAF inhibitors, alert your doctor as soon as possible.
MEK inhibitors also may be used to treat melanomas with BRAF gene mutations, sometimes in combination with BRAF inhibitors.
The FDA has approved a number of different testing methods designed to show whether a certain signaling pathway called MAPK has genetic mutations, including BRAF and NRAS mutations, which play a crucial role in the survival and development of melanoma tumor cells. Sections of your tumor may be mounted on slides and stained so that the tumor’s DNA can be analyzed under a microscope. Alternatively, a blood sample may be analyzed for circulating tumor DNA.
When your doctor sees your gene mapping results, he or she may order a genetic test to see whether you have an MEK gene mutation. If so, you may be prescribed an FDA-approved MEK inhibitor such as:
These targeted drugs are pills to be taken once or twice daily.
Your doctor is likely to prescribe an MEK inhibitor if your melanoma has spread or couldn’t be removed entirely with surgery.
MEK inhibitors also may be used to treat melanomas with BRAF gene mutations.
If your melanoma is stage 3, you may be given an MEK inhibitor and a BRAF inhibitor. This combination has been shown to be more beneficial than either alone. It also seems to lower the risk of developing other skin cancers.
Potential side effects of MEK inhibitors include:
Less common side effects include:
Trametinib may increase the risk of developing new skin and other cancers and decrease fertility in women.
Cobimetinib may decrease fertility in men and women.
Your doctor may stop your medication—temporarily or permanently—if you can’t tolerate the side effects.
Tell your doctor if you’re:
These drugs don’t require special diets. However, you should avoid grapefruit (whole or juice) while taking encorafenib and cobimetinib.
While on these drugs, avoid unnecessary exposure to the sun. Cover up with protective clothing. Use sunglasses, lip balm and sunscreen with an SPF of 30 or higher whenever you’re outside.
Patients given BRAF inhibitors to treat their metastatic melanoma seem to respond quickly. However, the response may not last as long as other immunotherapies. Some patients find it stops their disease from progressing further—at least for a number of months.
Combining immunotherapy with targeted therapies may improve response, though it may also increase the risk of more serious side effects.
Your doctor should monitor your skin and health closely while on these medications. You will likely need to see your doctor every two months while taking these inhibitors and continue follow-up appointments for at least six months after treatment.