Targeted radioiodine therapy of ovarian cancer via the sodium/iodide symporter (NIS).

OBJECTIVE

Ovarian cancer is the most lethal gynecological malignancy, but current treatments have not improved overall survival and recurrence rates. New therapies are needed and, in this context, we propose the use of the sodium/iodide symporter (NIS) that enables effective targeted Radioiodide therapy (RAI), as NIS is overexpressed in ovarian cancer.

METHODS

Using datasets and patient samples of human ovarian tumors, we determine the expression of NIS and canonical epithelial markers. We characterized NIS expression and function in human derived cell lines and tested the in vivo functional expression of NIS using Single Photon Emission Computed Tomography (SPECT). We also compared the efficacy of RAI versus chemotherapeutic treatments (cisplatin and paclitaxel) in mouse models.

RESULTS

Human ovarian tumors expressed NIS, predominantly in a non-glycosylated form, with plasma membrane localization. Datasets and RNAseq confirmed NIS expression in ovarian epithelial tumors. Functional NIS expression was observed both in vitro and in vivo. In preclinical ovarian cancer mouse models, RAI therapy with 131I greatly reduced or eliminated tumors, was more effective, and had fewer secondary effects than classical treatments (cisplatin and paclitaxel), although both could be combined.

CONCLUSIONS

Our findings highlight that RAI through NIS could serve as a therapeutic agent in ovarian cancer. Additionally, it may enable non-invasive imaging and monitoring of disease progression.