The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis

Abstract

Recent pre-clinical and clinical research has provided evidence that cancer progression is driven not only by a tumour's underlying genetic alterations and paracrine interactions within the tumour microenvironment, but also by complex systemic processes. We review these emerging paradigms of cancer pathophysiology and discuss how a clearer understanding of systemic regulation of cancer progression could guide development of new therapeutic modalities and efforts to prevent disease relapse following initial diagnosis and treatment.

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Figure 1: Composition of local and systemic tumour environments.
Figure 2: Mechanisms of systemic regulation of metastatic tumour cell extravasation and colonization.
Figure 3: Tumour-driven pathophysiological processes underlying cancer progression.

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Acknowledgements

All figures were conceptualized and created by Victor Fanjul (Universidad de Oviedo, Spain; former summer intern in the McAllister lab). We are grateful for the helpful discussions and/or editorial comments of Zvika Granot, Mikael Pittet and Yuval Shaked. S.S.M. is an American Cancer Society Scholar, an AACR Gertrude B. Elion Cancer Research Scholar and a Presidential Early Career Award for Scientists and Engineers scholar. R.A.W. is a Daniel K. Ludwig Professor for Cancer Research at MIT and an American Cancer Society Research Professor. This work was supported in part by grants from the National Institutes of Health (NCI) RO1 CA166284 and the American Cancer Society (S.S.M.); the Breast Cancer Research Foundation (BCRF), National Institutes of Health (NIH), R01 CA078461, P01 CA080111, and the Ludwig Center for Molecular Oncology at MIT (R.A.W.)

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Correspondence to Sandra S. McAllister or Robert A. Weinberg.

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McAllister, S., Weinberg, R. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol 16, 717–727 (2014) doi:10.1038/ncb3015

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