Our results showed that E2 regulates NRF2 via the binding of ERα to the ERE in the promoter of NRF2 upon bicalutamide treatment in PCa cells, indicating that NRF2 is a direct target gene of ERα and mediates bicalutamide resistance in CRPC as an ERα-mediated downstream effect of oestrogen. Here, ESR1 is linked to posterior cortical atrophy.