Dabrafenib response

Dabrafenib is a kinase inhibitor used in the treatment of patients with unresectable or metastatic melanoma with specific BRAF variants. Dabrafenib can be used as a single agent to treat melanoma with the BRAF V600E variant, or in combination with the MEK inhibitor trametinib to treat melanoma with BRAF V600E or V600K variants. BRAF is an intracellular kinase in the mitogen-activated protein kinases (MAPK) pathway. BRAF is involved in regulating important cell functions such as cell growth, division, differentiation, and apoptosis. BRAF is also a proto-oncogene—when mutated it has the ability to transform normal cells into cancerous cells. Variation in the kinase domain of BRAF have been associated with various cancers. The most common BRAF variant, V600E, constitutively activates the kinase, and causes cell proliferation in the absence of growth factors that would normally be required. The V600E variant is detected in approximately 50% of melanomas. The FDA-approved label for dabrafenib states that the presence of BRAF mutation in tumor specimens (V600E for dabrafenib monotherapy; V600E or V600K for dabrafenib plus trametinib) should be confirmed, using an FDA-approved test, before starting treatment with dabrafenib. Dabrafenib is not indicated for treatment of patients with wild-type BRAF melanoma. The label also states that patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency should be monitored for signs of hemolytic anemia while taking dabrafenib.

Medical Genetics Summaries