Introduction: Thyroid hormone (TH) metabolism is mediated by deiodinases, a family of thioredoxin fold-containing enzymes that remove iodide from thyroxine and its derivatives. The coordinated action of deiodinases allows target cells to modulate rapidly their own TH availability in response to different cues. Type 3 deiodinase (D3), the physiological inactivator of TH, is an oncofetal protein whose re-activation in adult tissues has been correlated with hyperproliferative states and with human solid tumors. This suggests a link between deiodinase-mediated TH metabolism and carcinogenesis.

Areas covered: D3 is overexpressed in basal cell carcinomas (BCCs) and sustains the proliferation of BCC cells. It exerts a similar function in colon cancer, which suggests that attenuating the TH signal is part of a widespread neoplastic program. Here, recent advances in D3 research, particularly as regards the role of D3 regulation and function in solid tumors are reviewed.

Expert opinion: Given the vast array of TH's physiological and cellular functions, unraveling TH metabolism in cancer biology is a promising challenge for the development of new therapies for human cancer.