European Medical Journal (Jun 2017)
Epithelial-Mesenchymal Transition in Docetaxel-Resistant Prostate Cancer
Abstract
Castration-resistant prostate cancer (CRPCa) is an advanced stage of prostate cancer in which a tumour progresses even under androgen deprivation. Treatment alternatives for CRPCa remain very limited and mostly rely on docetaxel-based chemotherapy. Despite being shown to increase patients’ overall survival, docetaxel’s clinical efficacy is impaired by development of chemoresistance. Most patients do not respond to docetaxel treatment and even those initially responsive ultimately develop resistance. Recently, chemoresistance was found to be closely related to epithelial-mesenchymal transition (EMT), a process in which epithelial cells transition into a mesenchymal phenotype. In fact, EMT markers are overexpressed in prostate cancer and are correlated to a higher Gleason score. For this reason, new therapeutic strategies are being studied to inhibit this process in several cancers. However, the clinical usefulness of targeting EMT as a way to overcome docetaxel resistance in CRPCa is still questionable and suffers from some significant limitations. This review briefly summarises the most common mechanisms of EMT-induced chemoresistance and evaluates its use as a new approach to overcome docetaxel resistance in CRPCa.
