Intronic Enhancer HRRINT3 Mediates Androgen Receptor Suppression of ER+ Breast Cancer Growth
A functional intronic enhancer, not the ZBTB16 coding sequence, transmits androgen receptor tumor suppression in ER+ breast cancer. CRISPR validation across cell models reveals a wider regulatory network with implications for AR agonist therapy. The finding supplies a molecular biomarker for patient selection and resistance monitoring.
Future studies must map HRRINT3 variants across patient cohorts and test whether enhancer-targeted epigenetic therapies can restore AR function in resistant tumors. Parallel CRISPR screens in patient-derived xenografts will clarify whether HRRINT3 deletion confers cross-resistance to CDK4/6 inhibitors. Within three years, incorporation of HRRINT3 status into trial stratification could refine selection for AR-directed regimens and improve progression-free survival endpoints.
Sources (3)
- [1]Primary Source(https://www.nature.com/articles/s41523-026-01037-5)
- [2]Supporting Source(https://www.nejm.org/doi/10.1056/NEJMoa2204750)
- [3]Supporting Source(https://www.science.org/doi/10.1126/science.abn0236)