Clinical and Biological Features of Neuroendocrine Prostate Cancer

AbstractPurpose of ReviewNeuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism of treatment resistance. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Here, we review the clinical and molecular features of NEPC based on recent studies and outline future strategies and directions.Recent FindingsNEPC can arise “de novo” but most commonly develops as a result of lineage plasticity whereby prostate cancer cells adopt alternative lineage programs as a means to bypass therapy. Dependence on androgen receptor (AR) signaling is lost as tumors progress from a prostate adenocarcinoma to a NEPC histology, typi cally manifested by the downregulation of AR, PSA, and PSMA expression in tumors. Genomic analyses from patient biopsies combined with preclinical modeling have pointed to loss of tumor suppressorsRB1 andTP53 as key facilitators of lineage plasticity. Activation of oncogenic drivers combined with significant epigenetic changes (e.g., EZH2 overexpression, DNA methylation) further drives tumor proliferation and expression of downstream neuronal and neuroendocrine lineage pathways controlled in part by pioneer and lineage determinant transcription factors (e.g., SOX2, ASCL1, BRN2). These biologic insights have provided a framework for the study of this subgroup of advanced prostate cancers and have start...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research