Figure 3.

Mechanism of RAI resistance and its reversal with targeted therapies. (A) Under normal conditions, expression of sodium-iodine symporter (NIS) is regulated through TSHR, resulting in stimulation of thyroid-specific transcriptional factors such as PAX8, which promotes NIS transcription and its expression on the cell surface. (B) In thyroid tumor cells with hyperactive MAPK and PI3K/AKT signaling, the NIS transcription is repressed, resulting in loss of its cell surface expression and RAI resistance. (C) Targeted treatment with inhibitors that block the MAPK/PI3K signaling pathways improves NIS expression and RAI avidity. * Trastuzumab has been tested in breast cancer model to target HER2 signaling but not in thyroid cancer model.