Tumour Microenvironment Stress Promotes the Development of Drug Resistance
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 chemothe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/11/1801 |
| _version_ | 1827677511569375232 |
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| author | Nicole A. Seebacher Maria Krchniakova Alexandra E. Stacy Jan Skoda Patric J. Jansson |
| author_facet | Nicole A. Seebacher Maria Krchniakova Alexandra E. Stacy Jan Skoda Patric J. Jansson |
| author_sort | Nicole A. Seebacher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:45:01Z |
| format | Article |
| id | doaj.art-43e84d073fb342e788c5a920837cdce9 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T05:45:01Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-43e84d073fb342e788c5a920837cdce92023-11-22T22:13:54ZengMDPI AGAntioxidants2076-39212021-11-011011180110.3390/antiox10111801Tumour Microenvironment Stress Promotes the Development of Drug ResistanceNicole A. Seebacher0Maria Krchniakova1Alexandra E. Stacy2Jan Skoda3Patric J. Jansson4Department of Oncology, University of Oxford, Oxford OX3 9DU, UKDepartment of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech RepublicCancer Drug Resistance & Stem Cell Program, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaDepartment of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech RepublicCancer Drug Resistance & Stem Cell Program, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaMulti-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.https://www.mdpi.com/2076-3921/10/11/1801tumour microenvironmental stressdrug resistancereactive oxygen speciescancer stem cells |
| spellingShingle | Nicole A. Seebacher Maria Krchniakova Alexandra E. Stacy Jan Skoda Patric J. Jansson Tumour Microenvironment Stress Promotes the Development of Drug Resistance Antioxidants tumour microenvironmental stress drug resistance reactive oxygen species cancer stem cells |
| title | Tumour Microenvironment Stress Promotes the Development of Drug Resistance |
| title_full | Tumour Microenvironment Stress Promotes the Development of Drug Resistance |
| title_fullStr | Tumour Microenvironment Stress Promotes the Development of Drug Resistance |
| title_full_unstemmed | Tumour Microenvironment Stress Promotes the Development of Drug Resistance |
| title_short | Tumour Microenvironment Stress Promotes the Development of Drug Resistance |
| title_sort | tumour microenvironment stress promotes the development of drug resistance |
| topic | tumour microenvironmental stress drug resistance reactive oxygen species cancer stem cells |
| url | https://www.mdpi.com/2076-3921/10/11/1801 |
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