# MAPK inhibitor redifferentiation → radioiodine

Source: https://onco.cc/pairings/redifferentiation-rai/  
OnCo record `redifferentiation-rai` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Small-molecule kinase inhibitors + Radioiodine therapy and whole-body iodine scanning
- Type: sequence
- 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.

## Sources

- ClinicalTrials.gov NCT01843062: ASTRA: https://clinicaltrials.gov/study/NCT01843062

## Connected records

- cancers: [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- technologies: [Radioiodine therapy and whole-body iodine scanning](https://onco.cc/technologies/radioiodine-therapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Radioactive iodine (I-131)](https://onco.cc/drugs/radioactive-iodine/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Radioiodine-refractory (RAI-R) thyroid cancer](https://onco.cc/terms/rai-refractory/)
- trials: [ASTRA](https://onco.cc/trials/astra/)

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