TY - JOUR
T1 - The role of epithelial plasticity in prostate cancer dissemination and treatment resistance
AU - Bitting, Rhonda L.
AU - Schaeffer, Daneen
AU - Somarelli, Jason A.
AU - Garcia-Blanco, Mariano A.
AU - Armstrong, Andrew J.
PY - 2014/9
Y1 - 2014/9
N2 - Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches.
AB - Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches.
KW - Dissemination
KW - Epithelial plasticity
KW - Epithelial-mesenchymal transition
KW - Metastasis
KW - Prostate cancer
KW - Stem cell
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U2 - 10.1007/s10555-013-9483-z
DO - 10.1007/s10555-013-9483-z
M3 - Article
C2 - 24414193
AN - SCOPUS:84905102552
SN - 0167-7659
VL - 33
SP - 441
EP - 468
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 2-3
ER -