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Review

Tumour Microenvironment Stress Promotes the Development of Drug Resistance

1
Department of Oncology, University of Oxford, Oxford OX3 9DU, UK
2
Department of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic
3
International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic
4
Cancer Drug Resistance & Stem Cell Program, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
5
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St. Leonards, NSW 2065, Australia
*
Authors to whom correspondence should be addressed.
Both authors contributed equally to this work as first authors.
Both authors contributed equally to this work as co-corresponding and senior authors.
Academic Editor: Vincenzo Ciminale
Antioxidants 2021, 10(11), 1801; https://doi.org/10.3390/antiox10111801
Received: 7 October 2021 / Revised: 29 October 2021 / Accepted: 8 November 2021 / Published: 11 November 2021
Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells. View Full-Text
Keywords: tumour microenvironmental stress; drug resistance; reactive oxygen species; cancer stem cells tumour microenvironmental stress; drug resistance; reactive oxygen species; cancer stem cells
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MDPI and ACS Style

Seebacher, N.A.; Krchniakova, M.; Stacy, A.E.; Skoda, J.; Jansson, P.J. Tumour Microenvironment Stress Promotes the Development of Drug Resistance. Antioxidants 2021, 10, 1801. https://doi.org/10.3390/antiox10111801

AMA Style

Seebacher NA, Krchniakova M, Stacy AE, Skoda J, Jansson PJ. Tumour Microenvironment Stress Promotes the Development of Drug Resistance. Antioxidants. 2021; 10(11):1801. https://doi.org/10.3390/antiox10111801

Chicago/Turabian Style

Seebacher, Nicole A., Maria Krchniakova, Alexandra E. Stacy, Jan Skoda, and Patric J. Jansson. 2021. "Tumour Microenvironment Stress Promotes the Development of Drug Resistance" Antioxidants 10, no. 11: 1801. https://doi.org/10.3390/antiox10111801

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