MAPK inhibitor redifferentiation → radioiodine

This sequence uses a short course of a small-molecule MAPK pathway inhibitor, such as selumetinib or dabrafenib with trametinib, to restore radioiodine uptake in radioiodine-refractory thyroid cancer, followed by treatment with radioactive iodine. MAPK signalling suppresses the sodium-iodide symporter, and blocking the pathway for four to six weeks re-expresses NIS, so the tumour takes up iodine again. Selumetinib, reported in NEJM in 2013, and later dabrafenib and trametinib restored uptake in a substantial share of refractory patients, especially those with RAS mutations, and durable responses followed in some; the evidence is multiple phase 2 series. The adjuvant version of the approach, tested in ASTRA, was negative, so redifferentiation is reserved for refractory disease.