Next Article in Journal
Letter from the New Editor-in-Chief
Next Article in Special Issue
Development of a Novel Enzyme-Targeting Radiosensitizer (New KORTUC) Using a Gelatin-Based Hydrogel Instead of a Sodium Hyaluronate
Previous Article in Journal
Profiling the Behavior of Distinct Populations of Head and Neck Cancer Stem Cells
Previous Article in Special Issue
Serial Assessment of Therapeutic Response to a New Radiosensitization Treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), in Patients with Stage I/II Breast Cancer Using Breast Contrast-Enhanced Magnetic Resonance Imaging
Article Menu

Export Article

Open AccessReview

Cancer Stem Cell Plasticity Drives Therapeutic Resistance

Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
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
Received: 19 October 2015 / Revised: 18 December 2015 / Accepted: 29 December 2015 / Published: 5 January 2016
(This article belongs to the Special Issue Drug/Radiation Resistance in Cancer Therapy)
PDF [778 KB, uploaded 5 January 2016]


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. View Full-Text
Keywords: cancer stem cells; therapeutic resistance; cellular plasticity; epithelial-mesenchymal; tumor microenvironment; cytokines cancer stem cells; therapeutic resistance; cellular plasticity; epithelial-mesenchymal; tumor microenvironment; cytokines

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top