MAP2K1 and melanoma: Acquired resistance most often occurs through downstream re-activation of the MAPK pathway through the release of negative feedback.15–19 This has led to the FDA approval of combined BRAF and MEK1/2 inhibition in melanoma.20–22 More recently, combined BRAF and MEK1/2 inhibition was approved for ATC based on a small phase II study of the BRAF inhibitor, dabrafenib (BRAFi), in combination with the MEK1/2 inhibitor, trametinib (MEKi), which showed a response rate of 69% in 16 BRAF-mutant ATC patients,14 seven of which were durable at the time of reporting.