The Molecular Basis for Radioiodine Therapy

Abstract

Radioactive iodine (radioiodine) therapy is a standard and effective therapeutic approach for high-risk differentiated thyroid carcinomas, based on the unique ability of the thyroid follicular cell to accumulate iodide through the sodium/iodide symporter (NIS). However, a recurrent limitation of radioiodine therapy is the development of radioiodine-refractory differentiated thyroid carcinomas, which are associated with a worse prognosis. Loss of radioiodine accumulation in thyroid carcinomas has been attributed to cell dedifferentiation, resulting in reduced NIS expression and NIS intracellular retention involving transcriptional and posttranscriptional or posttranslational mechanisms, respectively. Emerging therapies targeting the oncogene-activated signal pathways potentially involved in thyroid carcinogenesis have been able to recover radioiodine accumulation in radioiodine-refractory tumors, which constitutes the rationale of redifferentiation therapies. Here, we will comprehensively discuss the molecular mechanisms underlying radioiodine therapy, refractoriness to radioiodine therapy in differentiated thyroid carcinomas, and novel strategies for restoring radioiodine accumulation in radioiodine-refractory thyroid carcinomas.