1. ERβ in Triple-Negative Breast Cancer: Emerging Concepts and Therapeutic Possibilities
- Author
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Alessandra Monaco, Martina Di Gisi, Pia Giovannelli, Fabrizio Licitra, Marzia Di Donato, Gabriella Castoria, Antimo Migliaccio, Giovanni Galasso, Monaco, Alessandra, Licitra, Fabrizio, Di Gisi, Martina, Galasso, Giovanni, DI DONATO, Marzia, Giovannelli, Pia, Migliaccio, Antimo, and Castoria, Gabriella
- Subjects
Drug ,estrogen receptor β (ERβ) ,business.industry ,steroid receptors ,media_common.quotation_subject ,Context (language use) ,Drug resistance ,RC648-665 ,medicine.disease ,Diseases of the endocrine glands. Clinical endocrinology ,Androgen receptor ,Breast cancer ,triple negative breast cancer (TNBC) ,Cancer research ,medicine ,triple negative breast cancer (TNBC), estrogen receptor β (ERβ), steroid receptors, signal transduction ,Signal transduction ,business ,Estrogen receptor alpha ,signal transduction ,Triple-negative breast cancer ,media_common - Abstract
Despite the improvements in diagnostic and therapeutic approaches, breast cancer still remains one of the world’s leading causes of death among women. Particularly, triple negative breast cancer (TNBC) is characterized by aggressiveness, metastatic spreading, drug resistance and a very high percentage of death in patients. Nowadays, identification of new targets in TNBC appears very compelling. TNBC are considered negative for the estrogen receptor alpha (ERα) expression. Nevertheless, they often express ERβ and its variants. As such, this TNBC subtype still responds to estrogens. While the ERβ1 variant seems to act as a tumor-suppressor, the two variants ERβ2 and 5 exhibit pro-oncogenic activities in TNBC. Thus, ERβ1 activation might be used to limit the growth and spreading as well as to increase the drug sensitivity of TNBC. In contrast, the pro-oncogenic properties of ERβ2 and ERβ5 suggest the possible development and clinical use of specific antagonists in TNBC treatment. Furthermore, the role of ERβ might be regarded in the context of the androgen receptor (AR) expression, which represents another key marker in TNBC. The relationship between AR and ERβ as well as the ability to modulate the receptor-mediated effects through agonists/antagonists represent a challenge to develop more appropriate therapies in clinical management of TNBC patients. In this review, we will discuss the most recent data in the field. Therapeutic implications of these findings are also presented in the light of the discovery of specific ERβ modulators.
- Published
- 2021
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