Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance

Cell Stem Cell. 2019 Jan 3;24(1):65-78. doi: 10.1016/j.stem.2018.11.011. Epub 2018 Dec 13.


Our traditional understanding of phenotypic plasticity in adult somatic cells comprises dedifferentiation and transdifferentiation in the context of tissue regeneration or wound healing. Although dedifferentiation is central to tissue repair and stemness, this process inherently carries the risk of cancer initiation. Consequently, recent research suggests phenotypic plasticity as a new paradigm for understanding cancer initiation, progression, and resistance to therapy. Here, we discuss how cells acquire plasticity and the role of plasticity in initiating cancer, cancer progression, and metastasis and in developing therapy resistance. We also highlight the epithelial-to-mesenchymal transition (EMT) and known molecular mechanisms underlying plasticity and we consider potential therapeutic avenues.

Keywords: cancer; epithelial to mesenchymal transition; plasticity; therapy resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*