Nat Med: Androgen-like: anti-cancer factor for estrogen-positive breast cancer

During breast development, estrogen (ER) stimulates post-adolescent breast growth, whereas androgens (AR) inhibit the development process.
previous studies have shown that ER is necessary for breast development and drives most breast malignancies (about 80%), the role of AR is not yet clear.
the hormone-incompression in early breast tissue is not known, androgens have been used to treat breast cancer, and their efficacy is thought to be achieved by inhibiting hypothyroid-pituitary gland pathlines.
androgen therapy strategy was eventually terminated due to toxic side effects and the emergence of drugs that directly targeted ER.
currently, ER inhibitors are the standard treatment for ER-plus breast cancer, but the development of these drug resistance (endocrine resistance) is the leading cause of death in breast cancer patients.
therefore, androgen therapy may be a powerful tool in patient treatment alternatives.
androgen inhibits estrogen-induced cell proliferation in breast tissue, the role of AR in ER-positive breast cancer is still controversial, which limits the implementation of AR-targeted therapy.
In this study, researchers used a variety of clinically relevant cell line models and patient derivative models to confirm that AR activation rather than inhibition plays an effective anti-tumor activity in a variety of diseases, including resistance to ER and CDK4/6 inhibitors in standard treatments.
it is worth noting that the combined use of AR astrists with standard therapeutic drugs enhances the therapeutic response.
AR activity in primary ER-plus breast cancer clinical significance mechanism studies show that agonist activation ar can change the genome distribution of ER and the necessary co-activator factors (p300, SRC-3), resulting in the suppression of ER-regulated cell cycle genes, including known tumor suppressors, ar target gene expression levels were increased.
marker ar activity in more than one clinical ER-positive breast cancer queue can predict the survival of the disease.
in summary, the results provide clear evidence that AR has anti-cancer effects in ER-positive breast cancer, and that AR's agonists may be the best AR-oriented treatment strategy.