OncotargetFeb 23, 2018

Restoring iodine uptake in resistant thyroid cancer using a new drug found by screening for sodium iodide transporter enhancers

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 28, 2026

Abstract

K905-0266 TKI treatment significantly increased endogenous NIS expression in anaplastic thyroid cancer (ATC).

A high-throughput screening platform was developed to identify compounds that enhance sodium iodide symporter (NIS) expression.
K905-0266 TKI was selected as a potent enhancer of NIS, leading to increased accumulation of radioactive iodine (RAI).
Treatment with K905-0266 TKI resulted in decreased levels of phosphorylated-ERK, a signaling molecule associated with thyroid cancer progression.
Thyroid-metabolizing proteins were upregulated following K905-0266 TKI treatment, contributing to enhanced RAI accumulation.
K905-0266 TKI improved the therapeutic efficacy of RAI in ATC tumor models.

Simplified

Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid cancer (ATC) management, owing to the decrease in the endogenous sodium iodide symporter (NIS) expression. Therefore, new strategies for NIS re-induction are required to improve the efficacy of RAI therapy in ATC. In this study, we developed a novel high-throughput NIS enhancer screening platform using a dual reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and selected a new hit compound, K905-0266 TKI. The effects of K905-0266 TKI treatment was validated as RAI accumulation, changes in signalling pathway related to thyroid pathogenesis, and cytotoxicity of RAI depending on re-induction of endogenous NIS expression in ATC. Furthermore, we evaluated enhancement of NIS promoter and therapeutic efficacy of RAI in ATC tumour xenograft mice. After K905-0266 TKI treatment, the expression of endogenous NIS was significantly increased, while phosphorylated-ERK was decreased. In addition, the thyroid-metabolising protein expressions were upregulated and increased of RAI accumulation and its therapeutic effects in ATC. Moreover, K905-0266 TKI increased therapeutic efficacy of RAI in ATC tumour. In conclusion, we successfully established a novel high-throughput NIS enhancer screening platform to excavate a NIS enhancer and identified K905-0266 TKI among TKI candidates and it's proven to increase the endogenous NIS expression and therapeutic efficacy of RAI in ATC. These findings suggest that a novel high-throughput NIS enhancer screening platform is useful for selecting of NIS promoter enhancers. In addition, K905-0266 TKI can be used to re-induce endogenous NIS expression and recover RAI therapy in ATC. in vivo

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Restoring iodine uptake in resistant thyroid cancer using a new drug found by screening for sodium iodide transporter enhancers

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief