Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities

An incomplete view of the mechanisms that drive metastasis, the primary cause of cancer-related death, has been a major barrier to development of effective therapeutics and prognostic diagnostics. Increasing evidence indicates that the interplay between microenvironment, genetic lesions, and cellula...

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Veröffentlicht in:Genes & development 2019-10, Vol.33 (19-20), p.1295-1318
Hauptverfasser: Rambow, Florian, Marine, Jean-Christophe, Goding, Colin R
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container_issue 19-20
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container_title Genes & development
container_volume 33
creator Rambow, Florian
Marine, Jean-Christophe
Goding, Colin R
description An incomplete view of the mechanisms that drive metastasis, the primary cause of cancer-related death, has been a major barrier to development of effective therapeutics and prognostic diagnostics. Increasing evidence indicates that the interplay between microenvironment, genetic lesions, and cellular plasticity drives the metastatic cascade and resistance to therapies. Here, using melanoma as a model, we outline the diversity and trajectories of cell states during metastatic dissemination and therapy exposure, and highlight how understanding the magnitude and dynamics of nongenetic reprogramming in space and time at single-cell resolution can be exploited to develop therapeutic strategies that capitalize on nongenetic tumor evolution.
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Cell Plasticity
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Melanoma - physiopathology
Melanoma - therapy
Microphthalmia-Associated Transcription Factor - genetics
Microphthalmia-Associated Transcription Factor - metabolism
Neoplasm Metastasis - physiopathology
Neoplastic Stem Cells - cytology
Phenotype
Review
Tumor Microenvironment
title Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities
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