Lineage Plasticity in Cancer Progression and Treatment

Clémentine Le Magnen; Michael M. Shen; Cory Abate-Shen

doi:10.1146/annurev-cancerbio-030617-050224

Annual Review of Cancer Biology

Volume 2, 2018

Review Article

Free

Lineage Plasticity in Cancer Progression and Treatment

Clémentine Le Magnen¹, Michael M. Shen^1,2,3, and Cory Abate-Shen^1,2,4
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Affiliations: ¹Departments of Urology and Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA ²Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA; email: [email protected], [email protected] ³Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA ⁴Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA
Vol. 2:271-289 (Volume publication date March 2018) https://doi.org/10.1146/annurev-cancerbio-030617-050224
First published as a Review in Advance on December 01, 2017
© Annual Reviews

Abstract

Historically, it has been widely presumed that differentiated cells are determined during development and become irreversibly committed to their designated fates. In certain circumstances, however, differentiated cells can display plasticity by changing their identity, either by dedifferentiation to a progenitor-like state or by transdifferentiation to an alternative differentiated cell type. Such cellular plasticity can be triggered by physiological or oncogenic stress, or it can be experimentally induced through cellular reprogramming. Notably, physiological stresses that promote plasticity, such as severe tissue damage, inflammation, or senescence, also represent hallmarks of cancer. Furthermore, key drivers of cellular plasticity include major oncogenic and tumor suppressor pathways and can be exacerbated by drug treatment. Thus, plasticity may help cancer cells evade detection and treatment. We propose that cancer can be considered as a disease of excess plasticity, a notion that has important implications for intervention and treatment.

Keyword(s): cancer progression, differentiation, drug resistance, lineage plasticity, reprogramming, transdifferentiation

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