Cancer drug resistance induced by EMT: novel therapeutic strategies

© The Author(s) 2021.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.AF group has been supported by Plan Estatal I + D + i 2013 − 2016, co-funded by the Instituto de Salud Carlos III (ISCIII, Spain) under grant agreements PI13/00250 and PI18/00121 by Fondo Europeo de Desarrollo Regional (FEDER) “A way of Making Europe”; by “la Caixa” Foundation (ID 100010434) under the agreement (LCF/TR/CI19/52460016); by PRIS3 project from ACIS and Consolidation of Competitive Research (IN607B2020/14) from GAIN, both from Xunta de Galicia and by I.M.Q. San Rafael Foundation (A Coruña). The studies of IPW are supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Needham, MA, USA), the Sara and Natan Blutinger Foundation (West Orange, NJ, USA), the Fred August and Adele Wolpers Charitable Fund (Clifton, NJ, USA) and the James and Rita Leibman Endowment Fund for Cancer Research (New York, NY, USA). AB group is supported by the Croatian Science Foundation (CSF, Project No. IP-2016–06-1036). JDLR group is funded by the Instituto de Salud Carlos III (ISCIII, AES, Spain) with grants PI18/00591 and PT17/0009/0008, co-financed by the European Regional Development Fund (FEDER)