title: Modulation of sodium iodide symporter in thyroid cancer.
abstract: Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient's survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future.
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, 1645 Neil Avenue, 304 Hamilton Hall, Columbus, OH, 43210, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Lakshmanan
authors.forename: Daniel
authors.initials: D
authors.lastname: Scarberry
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Shen
authors.forename: Sissy M
authors.initials: SM
authors.lastname: Jhiang
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005818:Genetic Engineering; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D009362:Neoplasm Metastasis; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D013972:Thyrotropin / Q000378:metabolism; D015854:Up-Regulation; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters