Phenotype plasticity as enabler of melanoma progression and therapy resistance

Research output: Contribution to journalReview articlepeer-review

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)377-391
Number of pages15
JournalNature Reviews Cancer
Volume19
Issue number7
Early online date17 Jun 2019
DOIs
Publication statusPublished - 1 Jul 2019