Biomarcador Geral Mama Terapêutica

Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

Escrito por Carla Brito Lopes

Abstract

The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012.

This review considers first current treatment options:

surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer.

Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors.

Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells.

Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors.

The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology.

The clinical settings in which these novel drugs might have utility in the management of advanced breast cancer, and biomarkers for stratification of patients likely to benefit, are discussed. Finally, the potential side effects of the novel drugs on metabolism, osteoporosis, osteo-metastasis, and cachexia are considered.

 

Article first published online: 23 Mai 2014
DOI: http://dx.doi.org/10.2147/CMAR.S35024
© Cancer Management and Research

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Citation

[May FEB. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer. Cancer Manag Res. 2014 May 23;6:225-252. eCollection 2014].


This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License.

The full terms of the License are available at
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Sobre o autor

Carla Brito Lopes

Carla nasceu a 14 de Fevereiro de 1977 em Viana do Castelo. Completou o bacharelato em Anatomia Patológica, Citológica e Tanatológica na ESTES-Porto em 1998 e licenciou-se em 2001 pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016.
Actualmente encontra-se a frequentar mestrado em Genética Molecular e Biomedicina na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa.