Advanced melanoma traditionally has had poor prognosis with limited, modestly effective and relatively toxic systemic treatment options like cytotoxic chemotherapy (dacarbazine) and immunomodulating agents (high-dose interleukin-2 and ipilimumab) which have response rates of 6-20%. With the identification of BRAF mutations found to be present in 50% of melanomas and the clinical success of serine/threonine-protein kinase B-raf inhibitors the prognostic landscape of melanoma has changed considerably. Vemurafenib and dabrafenib have been at the forefront of antimelanoma-targeted agents with a tolerable side effect profile and efficacy that compared well with the standard chemotherapy. These characteristics have led to the regulatory approval of both agents for the treatment of melanoma. However, these agents are not curative and have a short life span primarily due to rapidly occurring drug resistance. More recently, mitogen-activated protein kinase kinase (MEK) inhibitors have been found to have strong anticancer activity independently as well as when combined with other agents like B-raf inhibitors due to their activity downstream of RAF. Preclinical data and limited clinical data suggest that MEK inhibitors may be a component of effective therapy for a broad spectrum of cancers with other oncogenic drivers.
Keywords: BRAF; MEK inhibitor; Melanoma; Targeted therapy; Trametinib.
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