Phenotype plasticity as enabler of melanoma progression and therapy resistance
AffiliationNavarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Publica de Navarra (UPNA), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), Pamplona, Spain
MetadataShow full item record
AbstractMalignant 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.
CitationArozarena I, Wellbrock C. Phenotype plasticity as enabler of melanoma progression and therapy resistance. Nat Rev Cancer. 2019 Jul;19(7):377-91.
JournalNature Reviews. Cancer
- Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma.
- Authors: Roesch A, Paschen A, Landsberg J, Helfrich I, Becker JC, Schadendorf D
- Issue date: 2016 May
- Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma.
- Authors: Falletta P, Sanchez-Del-Campo L, Chauhan J, Effern M, Kenyon A, Kershaw CJ, Siddaway R, Lisle R, Freter R, Daniels MJ, Lu X, Tüting T, Middleton M, Buffa FM, Willis AE, Pavitt G, Ronai ZA, Sauka-Spengler T, Hölzel M, Goding CR
- Issue date: 2017 Jan 1
- Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma.
- Authors: Jayachandran A, Anaka M, Prithviraj P, Hudson C, McKeown SJ, Lo PH, Vella LJ, Goding CR, Cebon J, Behren A
- Issue date: 2014 Jul 30
- Cancer drug addiction is relayed by an ERK2-dependent phenotype switch.
- Authors: Kong X, Kuilman T, Shahrabi A, Boshuizen J, Kemper K, Song JY, Niessen HWM, Rozeman EA, Geukes Foppen MH, Blank CU, Peeper DS
- Issue date: 2017 Oct 12
- Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.
- Authors: Ryu B, Kim DS, Deluca AM, Alani RM
- Issue date: 2007 Jul 4