Thyroid hormone signalling has been linked to prostate cancer, but the role of its main effector, thyroid hormone receptor β (TRβ), was unclear. This study conducted by Fesiuk et al. shows that the TRβ-selective antagonist NH-3 inhibits prostate cancer cell prolifertion in vitro and reduces tumour growth in LNCaP and 22Rv1 xenograft models, including the castration resistant 22Rv1 model, with no detectable toxicity. NH-3 lowers androgen receptor (AR) levels and AR target genes such as Nkx3.1 and PSA, outperforms enzalutamide, and acts synergistically with it. In patient data, THRB mRNA and TRβ protein are elevated in prostate cancer, and 74% of treatment-naïve tumours carry mutations in thyroid hormone signalling genes. The authors propose TRβ antagonists, alone or combined with enzalutamide, as a new strateg for castration-resistant disease, pending further validation.