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Regulation of Tumor Cell Dormancy by Tissue Microenvironments and Autophagy

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Systems Biology of Tumor Dormancy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 734))

Abstract

The development of metastasis is the major cause of death in cancer patients. In certain instances, this occurs shortly after primary tumor detection and treatment, indicating these lesions were already expanding at the moment of diagnosis or initiated exponential growth shortly after. However, in many types of cancer, patients succumb to metastatic disease years and sometimes decades after being treated for a primary tumor. This has led to the notion that in these patients residual disease may remain in a dormant state. Tumor cell dormancy is a poorly understood phase of cancer progression and only recently have its underlying molecular mechanisms started to be revealed. Important questions that remain to be elucidated include not only which mechanisms prevent residual disease from proliferating but also which mechanisms critically maintain the long-term survival of these disseminated residual cells. Herein, we review recent evidence in support of genetic and epigenetic mechanisms driving dormancy. We also explore how therapy may cause the onset of dormancy in the surviving fraction of cells after treatment and how autophagy may be a mechanism that maintains the residual cells that are viable for prolonged periods.

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Acknowledgements

This work is supported by grants from the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program, NIH/National Cancer Institute (CA109182, CA163131), NIEHS (ES017146), and NYSTEM to J.A.A-G, DoD Breast Cancer Postdoctoral Fellowship to M.S.S. and NIH RO1 CA126792, CA126792-S1 (ARRA), and a DOD BCRP Era of Hope Scholar Award (W81XWH-11-1-0310) to J.D.

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Authors and Affiliations

  1. Departments of Medicine and Otolaryngology, Tisch Cancer Institute, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, USA

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

  2. Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

    Jayanta Debnath MD

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  1. Maria Soledad Sosa PhD
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  2. Paloma Bragado PhD
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  3. Jayanta Debnath MD
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  4. Julio A. Aguirre-Ghiso PhD
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Correspondence to Julio A. Aguirre-Ghiso PhD .

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Editors and Affiliations

  1. St. Elizabeth's Medical Center, Tufts University School of Medicine, 145 Harrison Avenue, Boston, 02135, Massachusetts, USA

    Heiko Enderling

  2. , Center of Cancer Systems Biology, Tufts University School of Medicine, 736 Cambridge Street, Boston, 02135, Massachusetts, USA

    Nava Almog

  3. , Center of Cancer Systems Biology, Tufts University School of Medicine, 736 Cambridge Street, Boston, 02135, Massachusetts, USA

    Lynn Hlatky

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Sosa, M.S., Bragado, P., Debnath, J., Aguirre-Ghiso, J.A. (2013). Regulation of Tumor Cell Dormancy by Tissue Microenvironments and Autophagy. In: Enderling, H., Almog, N., Hlatky, L. (eds) Systems Biology of Tumor Dormancy. Advances in Experimental Medicine and Biology, vol 734. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1445-2_5

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