{"entity":{"id":"redifferentiation-rai","kind":"pairing","name":"MAPK inhibitor redifferentiation → radioiodine","aka":[],"tldr":"A short course of a MEK or BRAF pill can coax iodine-resistant thyroid cancer into taking up iodine again, letting radioactive iodine work once more.","summary":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01843062: ASTRA","url":"https://clinicaltrials.gov/study/NCT01843062"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["kinase-inhibitors","radioiodine-therapy"],"targets":[],"drugs":["radioactive-iodine","dabrafenib-trametinib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["rai-refractory"],"trials":["astra"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"kinase-inhibitors","b":"radioiodine-therapy","rationale":"MAPK signalling suppresses the sodium-iodide symporter; blocking it for 4-6 weeks re-expresses NIS.","evidence":"Multiple phase 2 series; ASTRA negative in the adjuvant setting.","pairingType":"sequence"},"route":"/pairings/redifferentiation-rai/","neighbours":{"cancer":[{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"technology":[{"id":"radioiodine-therapy","kind":"technology","name":"Radioiodine therapy and whole-body iodine scanning","route":"/technologies/radioiodine-therapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"radioactive-iodine","kind":"drug","name":"Radioactive iodine (I-131)","route":"/drugs/radioactive-iodine/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"rai-refractory","kind":"term","name":"Radioiodine-refractory (RAI-R) thyroid cancer","route":"/terms/rai-refractory/"}],"trial":[{"id":"astra","kind":"trial","name":"ASTRA","route":"/trials/astra/"}]}}