Tumour Microenvironment Stress Promotes the Development of Drug Resistance

被引:41
|
作者
Seebacher, Nicole A. [1 ]
Krchniakova, Maria [2 ,3 ]
Stacy, Alexandra E. [4 ]
Skoda, Jan [2 ,3 ]
Jansson, Patric J. [4 ,5 ]
机构
[1] Univ Oxford, Dept Oncol, Oxford OX3 9DU, England
[2] Masaryk Univ, Fac Sci, Dept Expt Biol, Brno 62500, Czech Republic
[3] St Annes Univ Hosp, Int Clin Res Ctr, Brno 65691, Czech Republic
[4] Univ Sydney, Sch Med Sci, Fac Med & Hlth, Canc Drug Resistance & Stem Cell Program, Camperdown, NSW 2006, Australia
[5] Univ Sydney, Kolling Inst, Fac Med & Hlth, Bill Walsh Translat Canc Res Lab, St Leonards, NSW 2065, Australia
关键词
tumour microenvironmental stress; drug resistance; reactive oxygen species; cancer stem cells; CANCER-ASSOCIATED FIBROBLASTS; INDUCIBLE FACTOR 1-ALPHA; HUMANIZED MONOCLONAL-ANTIBODY; I DOSE-ESCALATION; CELL LUNG-CANCER; CD4(+) T-CELLS; FACTOR-KAPPA-B; OXIDATIVE STRESS; BREAST-CANCER; UP-REGULATION;
D O I
10.3390/antiox10111801
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:32
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