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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.

Original publication

DOI

10.1101/gad.329771.119

Type

Journal article

Journal

Genes & development

Publication Date

10/2019

Volume

33

Pages

1295 - 1318

Addresses

Laboratory for Molecular Cancer Biology, Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Herestraat 49, 3000 Leuven, Belgium.

Keywords

Humans, Melanoma, Neoplasm Metastasis, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Phenotype, Microphthalmia-Associated Transcription Factor, Neoplastic Stem Cells, Tumor Microenvironment, Cell Plasticity