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  • Between Bedside and Bench
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Metastasis Awakening: Targeting dormant cancer

Nature Medicine volume 19, pages 276–277 (2013)Cite this article

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An important challenge for oncologists is to treat overt metastasis, the major source of cancer-related deaths1. Adjuvant therapy should prevent distant recurrences by targeting residual disseminated tumor cells (DTCs) that give origin to metastasis, as well as existing undetected micrometastasis. Whereas in some cases, such as breast cancer, patients can show delayed metastasis after hormonal therapies (for example, in estrogen receptor–positive tumors) or treatment with trastuzumab, for HER2 (also called ERBB2)-positive tumors2, adjuvant therapy is for the most part ineffective in fully blocking metastasis development and improving overall survival.

This may be explained by the fact that the biology of residual DTCs seems to diverge from that of the primary tumors and overt metastasis3. The usually unpredictable timing of metastasis can be due to the ability of DTCs to enter dormancy1. Dormant DTCs can in turn be refractory to targeted or conventional therapies2, further limiting treatment responses. Notably, more than 67% of deaths in patients with breast cancer occur after the 5-year survival mark, showing that residual disease can be dormant for very long periods1. This further argues that targeting dormant DTCs is crucial. Unfortunately, compared to other areas of cancer, our understanding of the biology of dormant residual DTCs is highly limited. Thus, 'bedside' clinical management of dormant disease will be a reality only after rigorous understanding of its molecular and cellular basis.

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Figure 1: Hypothetical scheme for DTC monitoring to treat dormant residual disease.

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Acknowledgements

Because of format and space limitations, we could not cite all the relevant literature. This work was supported by grants from the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program, NCI-CA109182, NCI-CA163131 and NYSTEM to J.A.A.-G and by US Department of Defense Breast Cancer Research Program grant 10904826 to M.S.S.

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Authors and Affiliations

  1. Paloma Bragado and Maria Soledad Sosa are in the Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Julio A. Aguirre-Ghiso, Tisch Cancer Institute, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York, USA.,

    Julio A Aguirre-Ghiso, Paloma Bragado & Maria Soledad Sosa

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  1. Julio A Aguirre-Ghiso
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  2. Paloma Bragado
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  3. Maria Soledad Sosa
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Correspondence to Julio A Aguirre-Ghiso.

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Aguirre-Ghiso, J., Bragado, P. & Sosa, M. Metastasis Awakening: Targeting dormant cancer. Nat Med 19, 276–277 (2013). https://doi.org/10.1038/nm.3120

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