BRAF-inhibitor therapy was explored across a spectrum of BRAF-mutated cancers and yielded high response rates in melanoma, non–small-cell lung cancer (NSCLC), and Langerhans cell histiocytosis but unanticipated resistance in colorectal cancer, despite ample preclinical evidence favoring efficacy.6,7 More recently, the US Food and Drug Administration (FDA) has approved the programmed death-1 inhibitor pembrolizumab for any patient with mismatch repair deficiency and high microsatellite instability. The gene discussed is BRAF; the disease is Langerhans cell histiocytosis.