DIO3 and cancer: However, as DIO3 is expressed at low levels in normal skin (31), this suggests that alternative pathways (e.g., epidermal or fibroblast growth factors or the Gli2-Shh pathway (16,32,33) are sustaining the expression and activity of this enzyme in skin tissue and lesions of RTHα patients, promoting local inactivation of TH, which is known to be pivotal in fostering cancer cell growth (16,34,35).