Advanced radioiodine-refractory differentiated thyroid cancer: the sodium iodide symporter and other emerging therapeutic targets

The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis

“…As TSH signaling is impaired during thyroid carcinogenesis, the miRNAs are able to escape from this TSH-mediated repression. In addition to the impairment of TSH signaling, TGFb and PI3K signaling are known to be hyperactivated in thyroid cancer (8,42). Thus, we suggest that aberrant signaling of key growth factors and cytokines (i.e., TSH, TGFb, and IGF1) are contributing to the strong upregulation of miR-146b seen in thyroid cancer (up to 35-fold).…”

“…We consistently show that miR-146b-3p binds to the 3 0 -UTR of NIS (site 3-9 nt), leading to an impaired translation of the protein and subsequently decreasing the iodide uptake of the cells. Several mechanisms have been proposed to explain NIS repression in thyroid cancer in order to establish new therapeutic approaches to try to reinduce iodide uptake (8,40). All of them are based on the transcriptional repression induced by aberrant signaling pathways and/or epigenetic events.…”

“…Radioactive iodide treatment is the most effectively targeted internal radiation anticancer therapy ever devised and it has been in use for over 60 years. Therefore, loss of the thyroid differentiated phenotype, particularly loss of NIS function, is one of the most important hallmarks of thyroid cancer progression, leading to iodide-refractory metastatic disease and a worse outcome of the patients (7,8).…”

Nodular Thyroid Disease and Thyroid Cancer in the Era of Precision Medicine

“…Although the aetiology of sodium iodide symporter loss of function is not completely understood, hyperactivation of some molecular pathways, such as the MAPK and the PI3K pathways, plays a primordial role [51] . Several approaches have been evaluated to restore the sodium iodide symporter action with the aim to reverse the refractoriness [52,53] .…”

18f-Fluorodeoxyglucose Positron Emission Tomography Combined With Computed Tomography in Evaluation of Effectiveness of Targeted Therapy of Radioactive Iodine-Refractory Differentiated Thyroid Cancer (Clinical Observation)

“…При прогрессировании опухолевого процесса биологические характеристики нормальной (фолликулярной) клетки щитовидной железы теряют-ся, в частности снижается содержание на мембране тиреоцитов белка-переносчика ионов йода -натрий-йодного симпортера, что приводит к потере способ-ности накапливать радиоактивный йод внутри клетки и, как следствие, к развитию радиойодрезистентности [3,4]. К другим независимым прогностическим фак-торам риска прогрессирования заболевания относят часто встречающуюся при папиллярном РЩЖ мутацию Опухоли ГОЛОВЫ и ШЕИ HEAD and NECK tumors Том 7 Vol.…”