Cited by 384Melanoma and MAPK PathwaysCancer Cells and MetastasisCutaneous Melanoma Detection and Management

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Phenotype plasticity as enabler of melanoma progression and therapy resistance

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Arozarena, Imanol, Wellbrock, Claudia·2019·Nature Reviews Cancer

DOI 10.1038/s41568-019-0154-4

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Abstract

Malignant melanoma is notorious for its inter- and intratumour heterogeneity, based on transcriptionally distinct melanoma cell phenotypes. It is thought that these distinct phenotypes are plastic in nature and that their transcriptional reprogramming enables heterogeneous tumours both to undergo different stages of melanoma progression and to adjust to drug exposure during treatment. Recent advances in genomic technologies and the rapidly expanding availability of large gene expression datasets have allowed for a refined definition of the gene signatures that characterize these phenotypes and have revealed that phenotype plasticity plays a major role in the resistance to both targeted therapy and immunotherapy. In this Review we discuss the definition of melanoma phenotypes through particular transcriptional states and reveal the prognostic relevance of the related gene expression signatures. We review how the establishment of phenotypes is controlled and which roles phenotype plasticity plays in melanoma development and therapy. Because phenotype plasticity in melanoma bears a great resemblance to epithelial-mesenchymal transition, the lessons learned from melanoma will also benefit our understanding of other cancer types.

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“Cell plasticity has been postulated to contribute to failure of chemo-, targeted- and immunotherapies (Arozarena and Wellbrock, 2019; Gupta et al., 2019; Horn et al., 2020).”
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Authors: Arozarena, I., & Wellbrock, C.
Affiliations: Universidad Pública de Navarra (UPNA) (ES)
University of Manchester (GB)
Corresponding author: Arozarena, Imanol
Wellbrock, Claudia
ORCID: Arozarena, Imanol
Wellbrock, Claudia
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2019-06-17
Volume: 19
Issue: 7
Pages: 377-391
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-019-0154-4
OpenAlex: W2950011075
Semantic Scholar: 92b52772c2e1273d54d8a8ce6b7911e17f048976
Cited by: 381
References: 155
Citations by year: 2026: 32 · 2025: 40 · 2024: 48 · 2023: 70 · 2022: 62 · 2021: 57 · 2020: 55 · 2019: 17
FWCI: 4.22
Type: journal article
Language: en
Open access: green
research.manchester.ac.uk
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion, other-oa)
Funders: Cancer Research UK (16416, C11591/A16416)
Instituto de Salud Carlos III (CP15/00176)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords: melanoma, phenotypic plasticity, melanoma progression, treatment resistance, targeted therapy resistance, immunotherapy resistance, tumor heterogeneity, gene expression signatures, transcriptional reprogramming, epithelial-mesenchymal transition, prognostic factors
MeSH terms: Adaptation, Physiological, Humans, Immunotherapy, Melanoma, Phenotype, Disease Progression, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition

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Phenotype plasticity as enabler of melanoma progression and therapy resistance

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