The Na + /I − symporter (NIS) is a plasma membrane protein that mediates the active transport of iodide (I − ) into the thyroid gland, a crucial first step in the biosynthesis of thyroid hormones. NIS is also the key target protein responsible for the high survival rates in metastatic thyroid cancer, achieved through the efficacy of radioiodide cancer treatments. The success of radiotherapy in NIS-expressing cancers raises the question of NIS's potential as a tool for treating non-NIS-expressing tumors. NIS also mediates electroneutral transport of the non-physiological substrates and environmental pollutants perchlorate (ClO 4 − ) and perrhenate (ReO 4 − ). This work focuses on engineering novel mutant NIS molecules that have broader treatment applications for cancer while also safeguarding healthy tissues. Specific mutations in NIS can modify its substrate transport selectivity, enabling the transport of radioactive oxyanions for potential cancer therapy without affecting those cells expressing wild-type (WT) NIS. These novel engineered NIS molecules could expand their therapeutic potential beyond traditional NIS-expressing tumors and pave the way for new treatment strategies for a variety of other cancers.
Llorente-Esteban et al. (Sun,) studied this question.