Cancer and Metastasis Reviews

, Volume 33, Issue 2–3, pp 441–468 | Cite as

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
Article

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.

Keywords

Epithelial plasticity Prostate cancer Metastasis Epithelial–mesenchymal transition Dissemination Stem cell 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rhonda L. Bitting
    • 1
    • 2
    • 3
  • Daneen Schaeffer
    • 3
    • 4
  • Jason A. Somarelli
    • 3
    • 4
  • Mariano A. Garcia-Blanco
    • 2
    • 3
    • 4
  • Andrew J. Armstrong
    • 1
    • 2
    • 3
    • 4
  1. 1.Division of Medical Oncology, Duke Cancer InstituteDuke UniversityDurhamUSA
  2. 2.Department of MedicineDuke UniversityDurhamUSA
  3. 3.Center for RNA BiologyDuke UniversityDurhamUSA
  4. 4.Department of Molecular Genetics and MicrobiologyDuke UniversityDurhamUSA

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