Prostate cancer stem cells: the role of androgen and estrogen receptors

Erika Di Zazzo, Giovanni Galasso, Pia Giovannelli, Marzia Di Donato, Annalisa Di Santi, Gustavo Cernera, Valentina Rossi, Ciro Abbondanza, Bruno Moncharmont, Antonio Agostino Sinisi, Gabriella Castoria _ and Antimo Migliaccio

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Oncotarget. 2016; 7:193-208. https://doi.org/10.18632/oncotarget.6220

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Erika Di Zazzo1, Giovanni Galasso1, Pia Giovannelli1, Marzia Di Donato1, Annalisa Di Santi1, Gustavo Cernera1, Valentina Rossi1, Ciro Abbondanza1, Bruno Moncharmont2, Antonio Agostino Sinisi3, Gabriella Castoria1 and Antimo Migliaccio1

1 Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy

2 Department of Medicine, University of Molise, Campobasso, Italy

3 Endocrinology Section, Department of Cardio-Thoracic and Respiratory Diseases, II University of Naples, Naples, Italy

Correspondence to:

Gabriella Castoria, email:

Keywords: prostate cancer; androgen receptor; estradiol receptors; GPR30, stem cells

Received: July 31, 2015 Accepted: September 30, 2015 Published: October 24, 2015


Prostate cancer is one of the most commonly diagnosed cancers in men, and androgen deprivation therapy still represents the primary treatment for prostate cancer patients. This approach, however, frequently fails and patients develop castration-resistant prostate cancer, which is almost untreatable.

Cancer cells are characterized by a hierarchical organization, and stem/progenitor cells are endowed with tumor-initiating activity. Accumulating evidence indicates that prostate cancer stem cells lack the androgen receptor and are, indeed, resistant to androgen deprivation therapy. In contrast, these cells express classical (α and/or β) and novel (GPR30) estrogen receptors, which may represent new putative targets in prostate cancer treatment.

In the present review, we discuss the still-debated mechanisms, both genomic and non-genomic, by which androgen and estradiol receptors (classical and novel) mediate the hormonal control of prostate cell stemness, transformation, and the continued growth of prostate cancer. Recent preclinical and clinical findings obtained using new androgen receptor antagonists, anti-estrogens, or compounds such as enhancers of androgen receptor degradation and peptides inhibiting non-genomic androgen functions are also presented. These new drugs will likely lead to significant advances in prostate cancer therapy.

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