Phenotype Switching: Tumor Cell Plasticity as a Resistance Mechanism and Target for Therapy
Abstract
Mutations in BRAF are present in the majority of patients with melanoma, rendering these tumors sensitive to targeted therapy with BRAF and MEK inhibitors. Unfortunately, resistance almost invariably develops. Recently, a phenomenon called "phenotype switching" has been identified as an escape route. By switching from a proliferative to an invasive state, melanoma cells can acquire resistance to these targeted therapeutics. Interestingly, phenotype switching bears a striking resemblance to the epithelial-to-mesenchymal-like transition that has been described to occur in cancer stem cells in other tumor types. We propose that these changes are manifestations of one and the same underlying feature, namely a dynamic and reversible phenotypic tumor cell plasticity that renders a proportion of cells both more invasive and resistant to therapy. At the same time, the specific characteristics of these tumor cell populations offer potential for being explored as target for therapeutic intervention.
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EMT is a phenotype switching event induced by targeted therapy in various tumors that has been linked to drug tolerance and/or resistance.
“For instance, epithelial-to-mesenchymal transition (EMT) is a phenotype switching event induced by targeted therapy in various tumors that has been linked to drug tolerance and/or resistance [78,79].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [79]
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- Authors
- Kemper, K., de Goeje, P. L., Peeper, D. S., & van Amerongen, R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- 1Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
- 2Section of Molecular Cytology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
- Venue
- Cancer Research
- Published
- 2014-10-30
- Volume
- 74
- Issue
- 21
- Pages
- 5937-5941
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2097469924
- Cited by
- 216
- References
- 40
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 12 · 2023: 14 · 2022: 16 · 2021: 32 · 2020: 28 · 2019: 22 · 2018: 19 · 2017: 16 · 2016: 21 · 2015: 22
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- phenotypic switching, tumor plasticity, melanoma, BRAF mutation, MEK inhibitors, targeted therapy resistance, epithelial-mesenchymal transition, cancer stem cells, tumor invasion, therapeutic target
- MeSH terms
- Humans, Mutation, Neoplasms, Neoplastic Stem Cells, Signal Transduction, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf
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