Dabrafenib.
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.
Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA, kainthla@bcm.edu.
Radhika
R
Kainthla
Kevin B
KB
Kim
Gerald S
GS
Falchook
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D010091:Oximes / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib