Cancer Stem Cell Plasticity Drives Therapeutic Resistance
1
Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
2
Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editors: Zhe-Sheng (Jason) Chen and Dong-Hua (Hana) Yang
Cancers 2016, 8(1), 8; https://doi.org/10.3390/cancers8010008
Received: 19 October 2015
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Revised: 18 December 2015
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Accepted: 29 December 2015
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Published: 5 January 2016
(This article belongs to the Special Issue Drug/Radiation Resistance in Cancer Therapy)
The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence.
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Keywords:
cancer stem cells; therapeutic resistance; cellular plasticity; epithelial-mesenchymal; tumor microenvironment; cytokines
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MDPI and ACS Style
Doherty, M.R.; Smigiel, J.M.; Junk, D.J.; Jackson, M.W. Cancer Stem Cell Plasticity Drives Therapeutic Resistance. Cancers 2016, 8, 8. https://doi.org/10.3390/cancers8010008
AMA Style
Doherty MR, Smigiel JM, Junk DJ, Jackson MW. Cancer Stem Cell Plasticity Drives Therapeutic Resistance. Cancers. 2016; 8(1):8. https://doi.org/10.3390/cancers8010008
Chicago/Turabian StyleDoherty, Mary R., Jacob M. Smigiel, Damian J. Junk, and Mark W. Jackson. 2016. "Cancer Stem Cell Plasticity Drives Therapeutic Resistance" Cancers 8, no. 1: 8. https://doi.org/10.3390/cancers8010008
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