Genetic and epigenetic alterations in the RTK/BRAF/MAPK/ERK and PI3K-AKT-mTOR pathways underly the diminished NIS signalling/activity that lead to RAI refractoriness and to a more aggressive behaviour (97): their identification can be useful to investigate new compounds able to act against these aberrant molecular mechanisms overcoming the standard cancer therapy resistance. The gene discussed is SLC5A5; the disease is cancer.