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Cellular plasticity and the neuroendocrine phenotype in prostate cancer.

TitleCellular plasticity and the neuroendocrine phenotype in prostate cancer.
Publication TypeJournal Article
Year of Publication2018
AuthorsDavies AH, Beltran H, Zoubeidi A
JournalNat Rev Urol
Date Published2018 Feb 20
ISSN1759-4820
Abstract

The success of next-generation androgen receptor (AR) pathway inhibitors, such as abiraterone acetate and enzalutamide, in treating prostate cancer has been hampered by the emergence of drug resistance. This acquired drug resistance is driven, in part, by the ability of prostate cancer cells to change their phenotype to adopt AR-independent pathways for growth and survival. Around one-quarter of resistant prostate tumours comprise cells that have undergone cellular reprogramming to become AR-independent and to acquire a continuum of neuroendocrine characteristics. These highly aggressive and lethal tumours, termed neuroendocrine prostate cancer (NEPC), exhibit reactivation of developmental programmes that are associated with epithelial-mesenchymal plasticity and acquisition of stem-like cell properties. In the past few years, our understanding of the link between lineage plasticity and an emergent NEPC phenotype has considerably increased. This new knowledge can contribute to novel therapeutic modalities that are likely to improve the treatment and clinical management of aggressive prostate cancer.

DOI10.1038/nrurol.2018.22
Alternate JournalNat Rev Urol
PubMed ID29460922