Narrative review: BRAF opens the door for therapeutic advances in melanoma.
Patients with metastatic melanoma have a poor prognosis and limited treatment options. In about one half of analyzed patients with metastatic melanoma, a mutated signal transduction molecule has been identified: v-raf murine sarcoma viral oncogene homolog B1 (BRAF). This molecule is part of an intracellular signaling cascade and may play a role in many different types of cancer. This article provides an overview of the current treatment options for metastatic melanoma and describes the pathophysiology underlying the development of therapies based on inhibition of BRAF. It summarizes findings of phase 1 and phase 2 studies of BRAF inhibitor therapy primarily in patients with metastatic melanoma, who have shown objective response rates of 70% to 80%. However, initial responses have not been sustained, with a median time to relapse of approximately 9 months. Clinicians should be aware of phase 3 trials of these agents and trials combining these therapies with other novel therapies because, at a minimum, BRAF inhibitors seem to be valuable as palliative therapy for metastatic melanoma.
Massachusetts General Hospital Cancer Center, Boston, 02114, USA. kflaherty@partners.org
Keith T
KT
Flaherty
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf