The potential clinical benefit of targeting androgen receptor (AR) in estrogen-receptor positive breast cancer cells treated with Exemestane

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Amaral, C (Author) Other; Augusto, TV (Author) Other; Almada, M (Author) Other; Cunha, SC (Author) Other; Correia da Silva, G (Author) Other; Teixeira, NA (Author) FFUP

Journal

Title: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1866

ISSN: 0925-4439

Publisher: Elsevier

Indexing

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Other information

Authenticus ID: P-00R-M4V

DOI: 10.1016/j.bbadis.2019.165661

Abstract (EN): The development of acquired resistance to the aromatase inhibitors (AIs) used in clinic is being considered the major concern in estrogen-receptor positive (ER+) breast cancer therapy. Recently, androgen receptor (AR) has gained attention in the clinical setting, since it has been implicated in AIs-resistance, although, different roles for AR in cell fate have been described. In this work, our group elucidates, for the first time, the oncogenic role of AR in sensitive and resistant ER+ breast cancer cells treated with the potent third-generation steroidal AI Exemestane (Exe). We demonstrate that Exe promotes an overexpression/activation of AR, which has an oncogenic and pro-survival role in Exe-sensitive and Exe-resistant cells. Moreover, we also disclose that targeting AR with bicalutamide (CDX) in Exe-treated cells, enhances the efficacy of this AI in sensitive cells and resensitizes resistant cells to Exe treatment. Furthermore, by targeting AR in Exe-resistant cells, it is also possible to block the activation of the ERK1/(2) and PI3K cell survival pathways, hamper ER alpha activation and increase ER beta expression. Thus, this study, highlights a new mechanism involved in Exe-acquired resistance, implicating AR as a key molecule in this setting and suggesting that Exe-resistant cells may have an AR-dependent but ER-independent mechanism. Hence we propose AR antagonism as a potential and attractive therapeutic strategy to overcome Exe-acquired resistance or to enhance the growth inhibitory properties of Exe on ER+ breast cancer cells, improving breast cancer treatment.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12