title: Epithelial-mesenchymal-transition regulators in prostate cancer: Androgens and beyond.
abstract: Castration resistant prostate cancer (CRPC) remains one of the leading causes of cancer deaths among men. Conventional therapies targeting androgen signaling driven tumor growth have provided limited survival benefit in patients. Recent identification of the critical molecular and cellular events surrounding tumor progression, invasion, and metastasis to the bone as well as other sites provide new insights in targeting advanced disease. Epithelial mesenchymal transition (EMT) is a process via which epithelial cells undergo morphological changes to a motile mesenchymal phenotype, a phenomenon implicated in cancer metastasis but also therapeutic resistance. Therapeutic targeting of EMT has the potential to open a new avenue in the treatment paradigm of CRPC through the reversion of the invasive mesenchymal phenotype to the well differentiated tumor epithelial tumor phenotype. Overcoming therapeutic resistance in metastatic prostate cancer is an unmet need in today's clinical management of advanced disease. This review outlines our current understanding of the contribution of EMT and its reversal to MET in prostate cancer progression and therapeutic resistance, and the impact of selected targeting of mechanisms of resistance via EMT towards a therapeutic benefit in patients with CRPC.
authors.affiliation: Departments of Urology, Biochemistry, Pathology and Toxicology & Cancer Biology, University of Kentucky College of Medicine, Lexington, KY, United States, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: Departments of Urology, Biochemistry, Pathology and Toxicology & Cancer Biology, University of Kentucky College of Medicine, Lexington, KY, United States, United States. Electronic address: nkypr2@uky.edu.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy; D011944:Receptors, Androgen / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D043823:Taxoids / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000728:Androgens; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D008024:Ligands; D011944:Receptors, Androgen; D051880:Receptors, Notch; D043823:Taxoids; D014157:Transcription Factors; D051153:Wnt Proteins
keywords: Androgen receptor; Cell plasticity; Epithelial transitions; Metastasis; Prostate cancer; Resistance; Therapeutic