During cancer progression, tumor cells undergo molecular and phenotypic changes collectively referred to as cellular plasticity. Such changes result from microenvironmental cues, stochastic genetic and epigenetic alterations, and/or treatment-imposed selective pressures, thereby contributing to tumor heterogeneity and therapy resistance. Epithelial-mesenchymal plasticity is the best-known case of tumor cell plasticity, but recent work has uncovered other examples, often with functional consequences. In this review, we explore the nature and role(s) of these diverse cellular plasticity programs in premalignant progression, tumor evolution, and adaptation to therapy and consider ways in which targeting plasticity could lead to novel anticancer treatments. SIGNIFICANCE: Changes in cell identity, or cellular plasticity, are common at different stages of tumor progression, and it has become clear that cellular plasticity can be a potent mediator of tumor progression and chemoresistance. Understanding the mechanisms underlying the various forms of cell plasticity may deliver new strategies for targeting the most lethal aspects of cancer: metastasis and resistance to therapy.
©2019 American Association for Cancer Research.