Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer

Most patients with differentiated thyroid cancer have a good prognosis after radioactive iodine-131 treatment, but there are still a small number of patients who are not sensitive to radioiodine treatment and may subsequently show disease progression. Therefore, radioactive-iodine refractory differentiated thyroid cancer treated with radioiodine usually shows reduced radioiodine uptake. Thus, when sodium iodine symporter expression, basolateral membrane localization and recycling degradation are abnormal, radioactive-iodine refractory differentiated thyroid cancer may occur. In recent years, with the deepening of research into the pathogenesis of this disease, an increasing number of molecules have become or are expected to become therapeutic targets. The application of corresponding inhibitors or combined treatment regimens for different molecular targets may be effective for patients with advanced radioactive-iodine refractory differentiated thyroid cancer. Currently, some targeted drugs that can improve the progression-free survival of patients with radioactive-iodine refractory differentiated thyroid cancer, such as sorafenib and lenvatinib, have been approved by the FDA for the treatment of radioactive-iodine refractory differentiated thyroid cancer. However, due to the adverse reactions and drug resistance caused by some targeted drugs, their application is limited. In response to targeted drug resistance and high rates of adverse reactions, research into new treatment combinations is being carried out; in addition to kinase inhibitor therapy, gene therapy and rutin-assisted iodine-131 therapy for radioactive-iodine refractory thyroid cancer have also made some progress. Thus, this article mainly focuses on sodium iodide symporter changes leading to the main molecular mechanisms in radioactive-iodine refractory differentiated thyroid cancer, some targeted drug resistance mechanisms and promising new treatments.