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  • Review Article
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EMT and cancer: what clinicians should know

Nature Reviews Clinical Oncology volume 22, pages 711–733 (2025)Cite this article

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Abstract

Cell plasticity is a crucial trait for cancer progression towards metastasis and treatment resistance. Research efforts from the past 20–30 years have revealed that the dynamic flux of the epithelial–mesenchymal transition (EMT) programme is one of the major underlying processes enabling cancer cell plasticity and greatly facilitates these major causes of cancer mortality. The spectrum of evidence ranges from extensive data from cell line and animal model studies across multiple cancer types through a rapidly expanding body of work demonstrating associations between EMT biomarkers and disease progression and mortality in patients. EMT is also implicated in resistance to most of the major treatment modalities, yet our efforts to harness this knowledge to improve therapeutic outcomes are currently in their early stages. In this Review, we describe clinical evidence supporting a role of EMT and the associated epithelial–mesenchymal plasticity in various stages of cancer in patients and discuss the subsequent clinical opportunities and challenges associated with attempts to implement this knowledge as novel therapies or clinical management approaches.

Key points

  • Cell plasticity is a crucial trait that supports the progression of a tumour towards metastatic dissemination and treatment resistance.

  • Partial and transient activation of the epithelial–mesenchymal transition (EMT) programme has an important role in enabling cancer cell plasticity.

  • Clinical data and analyses of human tumour tissue samples support a role of EMT and epithelial–mesenchymal plasticity (EMP) in many human cancer types.

  • EMT and EMP can influence all stages of cancer progression, from tumour initiation to the development of treatment resistance and metastases.

  • Interference with EMT and EMP is anticipated to offer various clinical opportunities.

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Fig. 1: Central mediators, properties and functions in EMP.
Fig. 2: Strategies to target EMP in cancer.

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Acknowledgements

The authors research is supported by the German Research Foundation (TRR305 TP A03, A04, B01 and B07, SPP2306 project 461704629 and BR1399/17-1, BR4145/1-1, BR4145/2-1 and BR4145/3-1), IZKF-Erlangen (IZKF D39), the Bavarian Cancer Research Center (BZKF:PRe-Ferro 001), the National Breast Cancer Foundation (Australia; RPG0118), and Tour de Cure (Australia; RSP-106-2024).

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  1. These authors contributed equally: Erik W. Thompson, Andrew D. Redfern, Marc P. Stemmler, Thomas Brabletz.

Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia

    Erik W. Thompson

  2. Translational Research Institute, Woolloongabba, Queensland, Australia

    Erik W. Thompson

  3. UWA Medical School, University of Western Australia, Crawley, Western Australia, Australia

    Andrew D. Redfern & Veenoo Agarwal

  4. Department of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany

    Simone Brabletz, Marc P. Stemmler & Thomas Brabletz

  5. Molecular and Cellular Oncology Laboratory, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

    Geert Berx

  6. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Karuna Ganesh

  7. School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ruby Y. Huang

  8. Oncology Institute, Shaba Medical Center, Ramat-Gan, Israel

    Dana Ishay-Ronen

  9. INSERM UMR 1186, Integrative Tumour Immunology and Immunotherapy, Gustave Roussy, Faculty of Medicine, University Paris-Saclay, Villejuif, France

    Pierre Savagner

  10. International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan

    Guojun Sheng

  11. Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Bavarian Cancer Research Center (BZKF), Erlangen, Germany

    Thomas Brabletz

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Contributions

E.W.T., A.D.R., S.B., V.A., M.P.S. and T.B. researched data for this manuscript. E.W.T., A.D.R., S.B., K.G., R.Y.H., D.I.-R., P.S., G.S., M.P.S. and T.B. made a substantial contribution to discussions of content. E.W.T., A.D.R., S.B., M.P.S. and T.B. wrote the manuscript. E.W.T., A.D.R., S.B., R.Y.H., D.I.-R., P.S., G.S., M.P.S. and T.B. edited and/or reviewed the manuscript prior to submission.

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Thompson, E.W., Redfern, A.D., Brabletz, S. et al. EMT and cancer: what clinicians should know. Nat Rev Clin Oncol 22, 711–733 (2025). https://doi.org/10.1038/s41571-025-01058-2

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