Inhibition of NR2F2 restores hormone therapy response to endocrine refractory breast cancers.

ABSTRACT: Endocrine resistance is frequently encountered in estrogen receptor-positive (ER+) breast cancer, often because of somatic mutations such as neurofibromin 1 (NF1) loss. The mechanisms by which ER-directed proliferation is lost in such cases are unknown, limiting the potential use of additional endocrine treatments. Here, we performed CRISPR-Cas9 knockout (KO) screens and found that nuclear receptor subfamily 2 group F member 2 (NR2F2), an orphan nuclear receptor, was essential for NF1 loss-induced endocrine resistance. Induction of NR2F2 was observed in ER+ cell line models and patient samples and occurred via activation of the mitogen-activated protein kinase (MAPK) pathway upon NF1 loss or other MAPK pathway genetic alterations. Mechanistically, increased NR2F

SUBMITTER: Cai Y 

PROVIDER: S-EPMC12662021 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature