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Marzagalli M, Montagnani Marelli M, Casati L, et al. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility. Front Endocrinol (Lausanne). 2016;7:140doi: 10.3389/fendo.2016.00140.
Marzagalli, M., Montagnani Marelli, M., Casati, L., Fontana, F., Moretti, R. M., & Limonta, P. (2016). Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility. Frontiers in endocrinology, 7140. https://doi.org/10.3389/fendo.2016.00140
Marzagalli, Monica, et al. "Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility." Frontiers in endocrinology vol. 7 (2016): 140. doi: https://doi.org/10.3389/fendo.2016.00140
Marzagalli M, Montagnani Marelli M, Casati L, Fontana F, Moretti RM, Limonta P. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility. Front Endocrinol (Lausanne). 2016 Oct 26;7:140. doi: 10.3389/fendo.2016.00140. eCollection 2016. PMID: 27833586; PMCID: PMC5080294.
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Front Endocrinol (Lausanne). 2016 Oct 26;7:140. doi: 10.3389/fendo.2016.00140. eCollection 2016.

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility.

Frontiers in endocrinology

Monica Marzagalli, Marina Montagnani Marelli, Lavinia Casati, Fabrizio Fontana, Roberta Manuela Moretti, Patrizia Limonta

Affiliations

  1. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano , Milano , Italy.
  2. Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano , Milano , Italy.

PMID: 27833586 PMCID: PMC5080294 DOI: 10.3389/fendo.2016.00140

Abstract

Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits.

Keywords: BRAF; ERβ; ERβ ligands; NRAS; melanoma; oncogenic mutations; phytoestrogens; targeted therapy

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