期刊
ARCHIVES OF TOXICOLOGY
卷 95, 期 7, 页码 2279-2297出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-021-03063-7
关键词
Epithelial plasticity; Cancer; Therapy resistance; Tumour microenvironment
类别
资金
- Instituto de Salud Carlos III (ISCIII, Spain) by Fondo Europeo de Desarrollo Regional (FEDER) A way of Making Europe [PI13/00250, PI18/00121]
- la Caixa Foundation [100010434, LCF/TR/CI19/52460016]
- Consolidation of Competitive Research from GAIN from Xunta de Galicia [IN607B2020/14]
- I.M.Q. San Rafael Foundation (A Coruna)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Needham, MA, USA)
- Sara and Natan Blutinger Foundation (West Orange, NJ, USA)
- Fred August and Adele Wolpers Charitable Fund (Clifton, NJ, USA)
- James and Rita Leibman Endowment Fund for Cancer Research (New York, NY, USA)
- Croatian Science Foundation (CSF) [IP-2016-06-1036]
- Instituto de Salud Carlos III (ISCIII, AES, Spain) [PI18/00591, PT17/0009/0008]
- European Regional Development Fund (FEDER)
- Plan Estatal I + D + i 2013 -2016
- PRIS3 project from ACIS from Xunta de Galicia [IN607B2020/14]
This review explores the important clinical benefits achieved in cancer patients through drug-targeting strategies, but drug resistance remains a major issue. The impact of epithelial-mesenchymal plasticity and tumor microenvironment on treatment effectiveness is discussed, along with the use of bioinformatics and pharmacogenomics to study the biological effects of epithelial-to-mesenchymal transition on drug resistance and develop novel pharmacological approaches in the future.
Over the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future.
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