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Metastasis prevention by targeting the dormant niche

Nature Reviews Cancer volume 15, pages 238–247 (2015)Cite this article

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Abstract

Despite considerable advancements that shattered previously held dogmas about the metastatic cascade, the evolution of therapies to treat metastatic disease has not kept up. In this Opinion article, I argue that, rather than waiting for metastases to emerge before initiating treatment, it would be more effective to target metastatic seeds before they sprout. Specifically, I advocate directing therapies towards the niches that harbour dormant disseminated tumour cells to sensitize them to cytotoxic agents. Treatment sensitization, achieved by disrupting reservoirs of leukaemic stem cells and latent HIV, argues that this approach, although unconventional, could succeed in improving patient survival by delaying or even preventing metastasis.

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Figure 1: Properties of dormant disseminated tumour cells are conferred by tissue-specific perivascular niches.
Figure 2: Parallels between stem cell regulation and the regulation of dormant disseminated tumour cells by the perivascular niche.
Figure 3: Two strategies to treat disseminated tumour cells.

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Acknowledgements

The author apologises to those whose invaluable contributions to the field were not cited owing to space limitations. The author is indebted to M. J. Bissell for the critical insights and endless conversation that formed the basis of this article, and for funding (from the National Cancer Institute (Award Number U54CA143836), U.S. Department of Defense Innovator Award (W81XWH0810736); and the Breast Cancer Research Foundation) that supported his time in her laboratory. The author's laboratory is partially supported by the National Cancer Institute (Award Number P50CA097186) and by the Cuyamaca Foundation. The author is very grateful to D. Lyden, C. Li, J. Bielas, and A. Bruni-Cardoso for their critical feedback on this manuscript, and to C. A. Grzelak for her advice on figures.

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  1. Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Cyrus M. Ghajar

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Ghajar, C. Metastasis prevention by targeting the dormant niche. Nat Rev Cancer 15, 238–247 (2015). https://doi.org/10.1038/nrc3910

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