The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

Rhonda L. Bitting, Daneen Schaeffer, Jason A. Somarelli, Mariano A. Garcia-Blanco, Andrew J. Armstrong

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)441-468
Number of pages28
JournalCancer and Metastasis Reviews
Volume33
Issue number2-3
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • Dissemination
  • Epithelial plasticity
  • Epithelial-mesenchymal transition
  • Metastasis
  • Prostate cancer
  • Stem cell

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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