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Tumor metastasis: moving new biological insights into the clinic

Abstract

As the culprit behind most cancer-related deaths, metastasis is the ultimate challenge in our effort to fight cancer as a life-threatening disease. The explosive growth of metastasis research in the past decade has yielded an unprecedented wealth of information about the tumor-intrinsic and tumor-extrinsic mechanisms that dictate metastatic behaviors, the molecular and cellular basis underlying the distinct courses of metastatic progression in different cancers and what renders metastatic cancer refractory to available therapies. However, integration of such new knowledge into an improved, metastasis-oriented oncological drug development strategy is needed to thwart the development of metastatic disease at every stage of progression.

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Figure 1: Models depicting the cellular and molecular basis in metastatic potential and progression.
Figure 2: The early steps of metastasis: tumor invasion, dissemination and survival in the circulation.

Debbie Maizels

Figure 3: Metastatic dormancy and reactivation in the lung.

Debbie Maizels

Figure 4: Tumor-stroma interactions at the primary site influence subsequent metastatic steps.

Debbie Maizels

Figure 5: Late steps of metastasis: niche formation, dormancy and colonization.

Debbie Maizels

Figure 6: Challenges and strategies for establishing multiple lines of defense against metastasis at different phases of tumor progression.

Debbie Maizels

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Acknowledgements

We thank members of our laboratories for helpful discussions and H.A. Smith for critical reading of the manuscript. We also apologize to the many investigators whose important studies could not be cited directly here because of space limitations. The work was supported by a Charlotte Elizabeth Procter Fellowship to L.W., grants from the European Research Council (Advanced Investigator Grant 'DISSECT'), the Deutsche Forschungsgemeinschaft and the German Minister of Education and Research (BMBF) to K.P. and grants from the Brewster Foundation, the Champalimaud Foundation, the US Department of Defense, Komen for the Cure and the US National Institutes of Health to Y.K.

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Wan, L., Pantel, K. & Kang, Y. Tumor metastasis: moving new biological insights into the clinic. Nat Med 19, 1450–1464 (2013). https://doi.org/10.1038/nm.3391

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