Emerging Therapeutics for Radioiodide-Refractory Thyroid Cancer

Abstract

Although uncommon, thyroid cancer constitutes the main endocrine neoplasia with an incidence rate that has been increasing steadily over the past decades. Recently, remarkable advances have occurred in understanding the biology of thyroid cancer. Novel germline and somatic point mutations as well as somatic chromosomal rearrangements associated with thyroid carcinogenesis have been discovered. Strikingly, acquired knowledge in the genetics of thyroid cancer has been translated into clinical practice, offering better diagnostic and prognostic accuracy and enabling the development of novel compounds for the treatment of advanced thyroid carcinomas. Even after 70 years, radioiodide therapy remains as the central treatment for advanced or metastatic differentiated thyroid cancer. However, the mechanisms leading to reduced radioiodide accumulation in the tumor cell remain partially understood. Radioiodide-refractory thyroid cancer metastasis constitutes a central problem in the management of thyroid cancer patients. In recent years, the antiangiogenic tyrosine kinase inhibitors sorafenib and lenvatinib have been approved for the treatment of advanced radioiodide-refractory thyroid carcinoma. Moreover, still on clinical phase of study, oncogene-specific and oncogene-activated signaling inhibitors have shown promising effects in recovering radioiodide accumulation in radioiodide-refractory thyroid cancer metastasis. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer. This review summarizes the latest advances in the understanding of the molecular basis of thyroid cancer, the mechanisms leading to reduced radioiodide accumulation in thyroid tumors and the results of clinical trials assessing emerging therapeutics for radioiodide-refractory thyroid carcinomas in the era of targeted therapies.