Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Seebacher, Nicole A., Krchniakova, Maria, Stacy, Alexandra E., Skoda, Jan, Jansson, Patric J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615091/
https://www.ncbi.nlm.nih.gov/pubmed/34829672
http://dx.doi.org/10.3390/antiox10111801
_version_ 1784604020751466496
author Seebacher, Nicole A.
Krchniakova, Maria
Stacy, Alexandra E.
Skoda, Jan
Jansson, Patric J.
author_facet Seebacher, Nicole A.
Krchniakova, Maria
Stacy, Alexandra E.
Skoda, Jan
Jansson, Patric J.
author_sort Seebacher, Nicole A.
collection PubMed
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 Online
Article
Text
id pubmed-8615091
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86150912021-11-26 Tumour Microenvironment Stress Promotes the Development of Drug Resistance Seebacher, Nicole A. Krchniakova, Maria Stacy, Alexandra E. Skoda, Jan Jansson, Patric J. Antioxidants (Basel) Review 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. MDPI 2021-11-11 /pmc/articles/PMC8615091/ /pubmed/34829672 http://dx.doi.org/10.3390/antiox10111801 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Seebacher, Nicole A.
Krchniakova, Maria
Stacy, Alexandra E.
Skoda, Jan
Jansson, Patric J.
Tumour Microenvironment Stress Promotes the Development of Drug Resistance
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615091/
https://www.ncbi.nlm.nih.gov/pubmed/34829672
http://dx.doi.org/10.3390/antiox10111801
work_keys_str_mv AT seebachernicolea tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance
AT krchniakovamaria tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance
AT stacyalexandrae tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance
AT skodajan tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance
AT janssonpatricj tumourmicroenvironmentstresspromotesthedevelopmentofdrugresistance