Targeted Therapy for Melanoma

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Melanoma specialist Paul Chapman with a patient

Medical oncologist Paul Chapman has led the development of therapies targeted to the genetic mutations found in melanoma tumors.

The DNA of a melanoma tumor usually contains many mutations. Mutations are changes in the sequence of a person’s DNA that can cause tumors to grow. One approach to melanoma treatment involves the use of drugs (also called therapies) that can target and disable the cells with these mutations. This, in turn, can cause tumors to shrink or grow less rapidly.

Researchers have identified several major genetic mutations associated with melanoma. BRAF mutations are the most common mutation found in tumor cells. They occur in about half of all melanomas. Other mutations identified in melanoma include ones that affect the NRAS, KIT, and GNAQ genes, to name a few.

BRAF Inhibitors for Metastatic Melanoma

Metastatic melanoma is cancer that has spread beyond its original location to other parts of the body. BRAF inhibitors are drugs that can shrink or slow the growth of metastatic melanoma in people whose tumors have a BRAF mutation. BRAF inhibitors include vemurafenib (Zelboraf®), dabrafenib (Tafinlar®), and encorafenib (Braftovi®).

MSK has taken a leadership role in the development of BRAF inhibitors for metastatic melanoma. In 2006, our doctors conducted the first clinical trial of vemurafenib, five years before the US Food and Drug Administration approved this treatment.

MSK experts are leading clinical trials to improve our ability to fight melanoma with BRAF inhibitors. Learn more about clinical trials for melanoma.

MEK Inhibitors Combined with BRAF Inhibitors for Metastatic Melanoma

The MEK gene has a close connection to the BRAF gene, so drugs that are targeted to MEK can also help treat melanoma with BRAF mutations. MEK inhibitors include trametinib (Mekinist®), cobimetinib (Cotellic®), and binimetinib (Mektovi®). 

The most common approach is to combine a MEK inhibitor with a BRAF inhibitor. This combination has been shown to be more effective than the use of either drug alone. When used together, BRAF and MEK inhibitors can shrink melanoma in the majority of people with BRAF-mutant melanoma.

Targeted Therapies for Other Mutations

Even when there is no BRAF mutation, there may be additional options to consider. Doctors at MSK are working to develop treatments for people with other mutations, such as NRAS and KIT.