Targeting p53 in melanoma

Abstract

Melanoma is the sixth most common cancer in the United States with the numbers of annual cases increasing faster than any other tumor type. Approximately 50% of melanomas harbor oncogenic BRAF mutations, 90% of which are BRAFV600E. Recently, US Food and Drug Administration (FDA) approval of the selective BRAFV600E inhibitor, Zelboraf (vemurafenib), has inspired rapid development of new targeted therapeutic strategies for melanoma. Subsequently, the first FDA approved combination of molecularly targeted cancer therapies has emerged with GlaxoSmithKline’s Tafinlar (dabrafenib) and Mekinist (trametinib) that inhibit BRAFV600E and the primary downstream target, MEK (mitogen-activated protein kinase kinase), respectively. As BRAF and MEK function within the same oncogenic RAS pathway, there is much anticipation about forthcoming clinical trials investigating molecularly targeted combination therapies that attack two or more different pathways.