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Unravelling the complexity of metastasis — molecular understanding and targeted therapies

Abstract

Despite recognizing the devastating consequences of metastasis, we are not yet able to effectively treat cancer that has spread to vital organs. The inherent complexity of genomic alterations in late-stage cancers, coupled with numerous heterotypic interactions that occur between tumour and stromal cells, represent fundamental challenges in our quest to understand and control metastatic disease. The incorporation of genomic and other systems level approaches, as well as technological breakthroughs in imaging and animal modelling, have galvanized the effort to overcome gaps in our understanding of metastasis. Future research carries with it the potential to translate the wealth of new knowledge and conceptual advances into effective targeted therapies.

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Figure 1: Research strategies for understanding the molecular basis of cancer metastasis: from reductionism to systems biology.
Figure 2: Evolving view of the dynamic relationship between the primary tumour and metastasis.

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Acknowledgements

The authors would like to thank members of their laboratory, particularly M. A. Blanco, for helpful discussions and critical comments on this manuscript. They apologize to those colleagues whose work is not cited owing to space limitations. The authors' research is funded by the Brewster Foundation, Champalimaud Foundation, American Cancer Society, Komen for the Cure, New Jersey Commission on Cancer Research, the US Department of Defense and the US National Institutes of Health (R01CA134519 and R01CA141062).

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Sethi, N., Kang, Y. Unravelling the complexity of metastasis — molecular understanding and targeted therapies. Nat Rev Cancer 11, 735–748 (2011). https://doi.org/10.1038/nrc3125

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