Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities
- 1Laboratory for Molecular Cancer Biology, Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Herestraat 49, 3000 Leuven, Belgium;
- 2Laboratory for Molecular Cancer Biology, Department of Oncology, KULeuven, Herestraat 49, B-3000 Leuven, Belgium;
- 3Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Headington, Oxford OX3 7DQ, United Kingdom
- Corresponding authors: colin.goding{at}ludwig.ox.ac.uk, jeanchristophe.marine{at}kuleuven.vib.be
Abstract
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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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.329771.119.
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