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...

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Autores principales:	Nicole A. Seebacher, Maria Krchniakova, Alexandra E. Stacy, Jan Skoda, Patric J. Jansson
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	tumour microenvironmental stress drug resistance reactive oxygen species cancer stem cells Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/43e84d073fb342e788c5a920837cdce9
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spelling	oai:doaj.org-article:43e84d073fb342e788c5a920837cdce92021-11-25T16:28:48ZTumour Microenvironment Stress Promotes the Development of Drug Resistance10.3390/antiox101118012076-3921https://doaj.org/article/43e84d073fb342e788c5a920837cdce92021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1801https://doaj.org/toc/2076-3921Multi-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.Nicole A. SeebacherMaria KrchniakovaAlexandra E. StacyJan SkodaPatric J. JanssonMDPI AGarticletumour microenvironmental stressdrug resistancereactive oxygen speciescancer stem cellsTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1801, p 1801 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumour microenvironmental stress drug resistance reactive oxygen species cancer stem cells Therapeutics. Pharmacology RM1-950
spellingShingle	tumour microenvironmental stress drug resistance reactive oxygen species cancer stem cells Therapeutics. Pharmacology RM1-950 Nicole A. Seebacher Maria Krchniakova Alexandra E. Stacy Jan Skoda Patric J. Jansson Tumour Microenvironment Stress Promotes the Development of Drug Resistance
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.
format	article
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
title	Tumour Microenvironment Stress Promotes the Development of Drug Resistance
title_short	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_sort	tumour microenvironment stress promotes the development of drug resistance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/43e84d073fb342e788c5a920837cdce9
work_keys_str_mv	AT nicoleaseebacher tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance AT mariakrchniakova tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance AT alexandraestacy tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance AT janskoda tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance AT patricjjansson tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance
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Tumour Microenvironment Stress Promotes the Development of Drug Resistance

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