The sodium iodide symporter (NIS) as theranostic gene: potential role in pre-clinical therapy of extra-thyroidal malignancies

Purpose Sodium iodide symporter (NIS), as a broadly exploited cancer theranostic molecule, has attracted considerable interest in non-thyroidal tumors. Several groups have investigated the significant potential of the NIS gene to induce radioiodine accumulation across various tumor types. In this review, we discuss the role of NIS as a theranostic gene in pre-clinical extra-thyroidal cancer therapy and highlight the remarkable progress in the viral and non-viral transgene transfer systems including oncolytic viruses, engineered mesenchymal stem cells (MSCs) and synthetic polyplexes. Methods A literature search was conducted using PubMed, Scopus, and Google Scholar databases. In addition, the keywords "sodium iodide symporter", "gene transfer", "extra-thyroidal malignancies", "viral transfer system", "non-viral transfer system", and " 131 I" were used. Results Following the exclusion of letters, editorials, commentaries, and duplicate publications, this review summarized preclinical studies that used viral and nonviral NIS delivery methods in conjunction with 131 I to describe the effective role of combination therapy. Conclusion NIS-mediated expression in combination with 131 I can be considered a promising approach in the preclinical treatment of extra-thyroidal malignancies and metastases. Malignant cells expressing NIS are thought to accumulate radionuclides intracellularly, which contributes to the remarkable therapeutic effects observed.