Prostate cancer stem cells: the role of androgen and estrogen receptors.
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.
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Erika
E
Di Zazzo
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Giovanni
G
Galasso
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Pia
P
Giovannelli
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Marzia
M
Di Donato
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Annalisa
A
Di Santi
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Gustavo
G
Cernera
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Valentina
V
Rossi
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Ciro
C
Abbondanza
Department of Medicine, University of Molise, Campobasso, Italy.
Bruno
B
Moncharmont
Endocrinology Section, Department of Cardio-Thoracic and Respiratory Diseases, II University of Naples, Naples, Italy.
Antonio Agostino
AA
Sinisi
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Gabriella
G
Castoria
Department of Biochemistry, Biophysics and General Pathology, II University of Naples, Naples, Italy.
Antimo
A
Migliaccio
D000728:Androgens / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008957:Models, Genetic; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
D000728:Androgens; C109584:GPER1 protein, human; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled
GPR30, stem cells; androgen receptor; estradiol receptors; prostate cancer