The potential clinical benefit of targeting androgen receptor (AR) in ER+ breast cancer cells treated with Exemestane

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The potential clinical benefit of targeting androgen receptor (AR) in ER+ breast cancer cells treated with Exemestane

Monday, 02.03.2020

 

Authors and Afiliations:

Cristina Amaral, Tiago V. Augusto, Marta Almada, Sara C. Cunha, Georgina Correia-da-Silva, Natércia Teixeira

UCIBIO.REQUIMTE, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto

 

Abstract:

The development of acquired resistance to the aromatase inhibitors (AIs) used as first-line treatment approach is nowadays considered the major clinical concern in ER+ breast cancer therapy. In the last years, our group has been focused in understanding the molecular mechanisms behind the acquired resistance to AIs in order to discover new therapeutic targets or strategies that may improve breast cancer therapy. Recently, androgen receptor (AR) modulation has gained attention in the clinical setting and, in fact, some clinical trials are underway to study the effectiveness of combining AIs with AR modulators, nevertheless the results are not yet known. In this work, we have described, for the first time, the oncogenic role of AR in sensitive and resistant ER+ breast cancer cells treated with the steroidal AI Exemestane. A new mechanism involved in Exemestane-acquired resistance was elucidated, implicating AR as a key molecule in this setting and, therefore, an attractive therapeutic target. Thus, we have studied the potential clinical benefit of combining Exemestane with the AR modulator Bicalutamide, in an attempt to support the ongoing clinical trials and to unveil the molecular mechanisms associated to this combination. It was demonstrated that by targeting AR it is possible to overcome Exemestane-acquired resistance and, thus, to enhance the clinical effectiveness of Exemestane. Thus, with this work, our group proposes AR antagonism as a potential and attractive therapeutic strategy to improve ER+ breast cancer treatment.

 

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

 

Linkhttps://www.sciencedirect.com/science/article/abs/pii/S0925443919303928