Issues

Dahlman and colleagues identified a BRAF^L597R mutation in an aggressive BRAF^V600E-negative melanoma, and found that as many as 8% of melanomas classified clinically as “BRAF wild type” may actually harbor other less common BRAF exon 15 mutations. Importantly, these mutants led to increased MEK/ERK signaling that was readily suppressed by MEK inhibitors, suggesting that patients with these less common BRAF mutations may also benefit from MEK inhibitor therapy. Indeed, one such patient with metastatic melanoma enrolled in a phase I trial of an allosteric MEK inhibitor experienced a sustained partial response, indicating that expanded BRAF mutational testing may benefit additional patients. For details, please see the article by Dahlman and colleagues on page 791.