Heme oxygenase-1 in thyroid cancer: a context-dependent regulator.

PURPOSE: Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step of heme degradation and has traditionally been regarded as a cytoprotective, antioxidant enzyme. However, HO-1 also influences tumour behaviour through activities independent of its catalytic function. This review aims to integrate current evidence on HO-1 regulation and function in thyroid cancer and to examine how its context-dependent actions may influence tumour biology and therapeutic response. METHODS: We review available preclinical and clinical evidence on HO-1 in thyroid cancer, with particular emphasis on oxidative stress, metabolic reprogramming, tumour progression, subcellular localization, and the potential therapeutic implications of HO-1 modulation. RESULTS: Current evidence links HO-1 to proliferation, redox homeostasis, and metabolic flexibility in thyroid cancer. Importantly, its effects are not uniform but appear to depend on tumour subtype, cellular context, structural state, and intracellular compartment. In particular, nuclear HO-1 may mediate non-enzymatic functions associated with more aggressive and treatment-refractory phenotypes. Although modulation of HO-1 has potential therapeutic relevance, supporting evidence remains predominantly preclinical. CONCLUSION: HO-1 should not be considered solely as an antioxidant enzyme in thyroid cancer, but rather as a context-dependent regulator whose functional output is shaped by tumour context and subcellular localization. Further clinical validation is required to establish its prognostic and therapeutic relevance.