Can Androgen Receptor Agonists Improve Outcomes in Estrogen Receptor–Positive Breast Cancer?
Posted: Wednesday, February 24, 2021
For patients with estrogen receptor-α–positive breast cancer, androgens may serve as a novel therapeutic option, according to a study published in Nature Medicine. Although androgen receptors have been explored as a possible target for pharmacologic therapy, the increased side effects deterred continued exploration of this route. Nonetheless, the need for new therapeutic alternatives led authors to re-explore the efficacy of androgen receptor therapy, explained Wayne D. Tilley, PhD, of the Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide, South Australia, and colleagues.
“This work has immediate implications for women with metastatic estrogen receptor–positive breast cancer, including those resistant to current forms of endocrine therapy,” commented study co-author Theresa E. Hickey, PhD, also of the University of Adelaide, in an institutional press release.
To determine whether androgen receptors could be used as pharmacologic targets, breast tissue samples were obtained from the Flinders Medical Centre. In addition, standard cell-line tissues were used for comparison. Tissues were subjected to many laboratory assessments, including immunohistochemistry, RNA sequencing, and immunoblotting, to isolate differences in receptor expression and function.
The authors determined that androgen receptor activation played a significant role in antitumor activity across multiple disease contexts. In addition, the combined therapy of androgen receptor agonists and standard-of-care pharmacologic treatments led to improved outcomes. Further analysis revealed that androgen receptor agonists altered estrogen receptor and co-activators p300 and SRC-3 genomic distribution. This alteration resulted in the upregulation of androgen receptor genes involved in tumor suppression. Furthermore, the effect of androgen receptor activity improved outcomes in numerous patients with estrogen receptorpositive breast cancer. These findings support the exploration of androgen receptor agonists as a potential therapeutic option for patients with this subtype of breast cancer.
Disclosure: For full disclosures of the study authors, visit nature.com.
