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BRAF in metastatic melanoma

Human cancers arise through a multistage process, often driven by genetic mutations that stimulate tumor cell proliferation and cell survival. Many of these activating mutations are restricted to particular cell lineages and so are linked to particular types of cancer. An example of this is seen in melanoma with BRAF, a protein kinase of the mitogen-activated protein kinase (MAPK) pathway, which normally regulates cell growth, proliferation, and differentiation.^14,15

Melanoma is a complex genetic disease, and multiple genetic alterations have been reported to play a role during disease progression. The dysregulation of BRAF signaling has been shown to be one of these key drivers of the disease. In 2002, Davies et al first reported that BRAF is mutated in approximately 8% of human tumors, most frequently in melanoma where the BRAF^V600 mutation is observed in approximately 50% of tumors. Mutations in BRAF^V600E may cause the protein to become oncogenic. In preclinical studies, oncogenic BRAF signaling that is a result of this mutation may lead to increased and uncontrolled cell proliferation and resistance to apoptosis (programmed cell death).^3,6,15

Since the discovery of BRAF^V600E mutations in melanoma in 2002, scientists and clinicians have learned much about the role of mutated BRAF^V600E, but many questions remain unanswered and research is ongoing. The rapidly increasing incidence of melanoma, coupled with its highly aggressive metastatic nature and limited current treatment options, make this an active and exciting area of research.¹⁵

Metastatic melanoma is a rapidly progressing disease with an 8-month median overall survival and a 25% 1-year survival rate. Current therapies include chemotherapy, radiotherapy, and immunotherapy.^8,13,16

Click one of the topics below to learn more about the role of oncogenic BRAF in melanoma:

• Oncogenic BRAF is involved in various stages of melanoma development
• Oncogenic BRAF is expressed in a variety of melanoma subtypes
• Oncogenic BRAF expression is associated with poor prognosis in metastatic melanoma and other solid tumors
• Identifying BRAF^V600E mutations in melanoma