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Cancers 2018, 10(12), 471;

Chemoresistance and the Self-Maintaining Tumor Microenvironment

Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK
Author to whom correspondence should be addressed.
Gulcen Yeldag and Alistair Rice contributed equally to this paper.
Received: 8 November 2018 / Revised: 24 November 2018 / Accepted: 27 November 2018 / Published: 28 November 2018
(This article belongs to the Special Issue Cancer Chemoresistance)
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The progression of cancer is associated with alterations in the tumor microenvironment, including changes in extracellular matrix (ECM) composition, matrix rigidity, hypervascularization, hypoxia, and paracrine factors. One key malignant phenotype of cancer cells is their ability to resist chemotherapeutics, and elements of the ECM can promote chemoresistance in cancer cells through a variety of signaling pathways, inducing changes in gene expression and protein activity that allow resistance. Furthermore, the ECM is maintained as an environment that facilitates chemoresistance, since its constitution modulates the phenotype of cancer-associated cells, which themselves affect the microenvironment. In this review, we discuss how the properties of the tumor microenvironment promote chemoresistance in cancer cells, and the interplay between these external stimuli. We focus on both the response of cancer cells to the external environment, as well as the maintenance of the external environment, and how a chemoresistant phenotype emerges from the complex signaling network present. View Full-Text
Keywords: chemoresistance; ECM; fibrosis; hypoxia; mechanosignaling; paracrine; hypervascularization; cancer stem cells chemoresistance; ECM; fibrosis; hypoxia; mechanosignaling; paracrine; hypervascularization; cancer stem cells

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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).

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Yeldag, G.; Rice, A.; Del Río Hernández, A. Chemoresistance and the Self-Maintaining Tumor Microenvironment. Cancers 2018, 10, 471.

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