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

Piyush B Gupta; Ievgenia Pastushenko; Adam Skibinski; Cedric Blanpain; Charlotte Kuperwasser

doi:10.1016/j.stem.2018.11.011

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.

Authors

Piyush B Gupta¹, Ievgenia Pastushenko², Adam Skibinski³, Cedric Blanpain⁴, Charlotte Kuperwasser⁵

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: piyush@mit.edu.
² Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels 1070, Belgium.
³ Department of Developmental, Chemical and Molecular Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA; Raymond and Beverly Sackler Convergence Laboratory, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St., Boston, MA 02111, USA.
⁴ Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels 1070, Belgium; WELBIO, Université Libre de Bruxelles, Brussels 1070, Belgium. Electronic address: cedric.blanpain@ulb.ac.be.
⁵ Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels 1070, Belgium; Department of Developmental, Chemical and Molecular Biology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA; Raymond and Beverly Sackler Convergence Laboratory, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA. Electronic address: charlotte.kuperwasser@tufts.edu.

Abstract

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*

Abstract

Publication types

MeSH terms

Grants and funding