Selectively Targeting Mutant BRAF in Thyroid Cancer

Abstract

Salerno et al. (1) in this issue of the Journal present the first preclinical thyroid cancer studies to use a promising category of targeted therapy, drugs that selectively inhibit the mutant BRAF oncoprotein. BRAF has occupied a central role in thyroid cancer pathogenesis since the original identification of BRAF mutations in papillary and anaplastic thyroid cancer (2, 3). Numerous follow-up studies have shown an adverse impact on prognosis of the predominant V600E mutation (4, 5). This molecular lesion is present in about 40% of papillary and 25% of anaplastic lesions and usually appears without other simultaneous molecular changes in the canonical ras-RAF-MAPK kinase (MEK)-ERK pathway (3). BRAF mutations correlate strongly with radioiodine resistance and reduced expression of the sodium iodide symporter (6).