Dabrafenib.

ABSTRACT

Dabrafenib was developed as a highly specific reversible inhibitor of V600-mutant BRAF kinase, an oncogenic mutation driving proliferation in many different types of aggressive tumors. Metastatic melanoma has a high prevalence of V600-mutant BRAF, and clinical trials showed that dabrafenib improved response rates and median progression-free survival in patients with V600E BRAF mutations, including those with brain metastasis. Preliminary results suggest that dabrafenib may also have some role in non-melanoma V600-mutant solid tumors; however, more studies are needed. With a well-tolerated toxicity profile and few drug interactions, dabrafenib is effective as a monotherapy; however, resistance eventually develops in most patients after persistent exposure to the drug. Current research focuses on combination strategies with dabrafenib to not only improve response rates but also overcome resistance.