Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance
Piyush B Gupta1, Ievgenia Pastushenko2, Adam Skibinski3
1Whitehead 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.
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.
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