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The current paradigm and challenges ahead for the dormancy of disseminated tumor cells

Abstract

Disseminated tumor cells (DTCs) are known to enter a state of dormancy that is achieved via growth arrest of DTCs and/or a form of population equilibrium state, strongly influenced by the organ microenvironment. During this time, expansion of residual disseminated cancer is paused and DTCs survive to fuel relapse, sometimes decades later. This notion has opened a new window of opportunity for intervening and preventing relapse. Here we review recent data that have further augmented the understanding of cancer dormancy and discuss how this is leading to new strategies for monitoring and targeting dormant cancer.

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Fig. 1: Differences and commonalities among normal quiescent, senescent, differentiated cells and dormant cancer cells.
Fig. 2: The various BM niches, cell types and cues that regulate the dormancy of DTCs and HSCs.
Fig. 3: Cues, receptors and cell types involved in DTC reactivation and pro-dormancy niches.

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Acknowledgements

We thank the Aguirre-Ghiso and Maguer-Satta labs for useful discussions during the preparation of this article. E.R. is supported by a doctoral fellowship from the University of Lyon, France, and by CLARA and IDEX Lyon mobility fellowships. E.R., A.R.N. and J.A.A.-G. are supported by grants CA109182, CA218024, CA216248 and CA196521 from the US National Institutes of Health; the Jimmy V Foundation; the Falk Medical Research Trust; HiberCell; and Metavivor. J.A.A.-G. is a Samuel Waxman Cancer Research Foundation Investigator. V.M.S. is supported by grants from ‘Fondation de France’ 2014-0047501 and 2017-00076282/Fondation Ramona Ehrman Amador, ‘Association Laurette Fugain’ ALF2014-03, Ligue contre le Cancer (Haute Savoie, Loire, Puy de Dôme and Rhone), ‘Association ALTE-SMP’ and the Institut Convergence PLASCAN.

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Correspondence to Julio A. Aguirre-Ghiso.

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Risson, E., Nobre, A.R., Maguer-Satta, V. et al. The current paradigm and challenges ahead for the dormancy of disseminated tumor cells. Nat Cancer 1, 672–680 (2020). https://doi.org/10.1038/s43018-020-0088-5

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  • DOI: https://doi.org/10.1038/s43018-020-0088-5

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