Systems Biology of Tumor Dormancy

Volume 734 of the series Advances in Experimental Medicine and Biology pp 145-179


Tumor Dormancy and Cancer Stem Cells: Two Sides of the Same Coin?

  • Sonja KleffelAffiliated withHarvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital, Harvard Institutes of Medicine
  • , Tobias SchattonAffiliated withHarvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital, Harvard Institutes of Medicine Email author 

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Increasing evidence suggests that tumor dormancy represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to its more established role in maintaining minimal residual disease after treatment, dormancy might also critically contribute to early stages of tumor development and the formation of clinically undetectable micrometastatic foci. There are striking parallels between the concept of tumor dormancy and the cancer stem cell (CSC) theory of tumor propagation. For instance, the CSC hypothesis similarly predicts that a subset of self-renewing cancer cells—that is CSCs—is responsible for tumor initiation, bears the preferential ability to survive tumor therapy, and persists long term to ultimately cause delayed cancer recurrence and metastatic progression. Additionally, many of the biological mechanisms involved in controlling the dormant state of a tumor can also govern CSC behavior, including cell cycle modifications, alteration of angiogenic processes, and modulation of antitumor immune responses. In fact, quiescence and immune escape are emerging hallmark features of at least some CSCs, indicating significant overlap between dormant cancer populations and CSCs. Herein, we crucially dissect whether CSCs occupy specific roles in orchestrating the switch between dormancy and exuberant tumor growth. We elucidate how recently uncovered CSC biological features could enable these cells to evade immunologic clearance and regulate cancer expansion, relapse, and progression. We propose that the study of CSC immunobiological pathways holds the promise to critically advance our understanding of the processes mediating tumor dormancy. Ultimately, such research endeavors could unravel novel therapeutic avenues that efficiently target both proliferating and dormant CSCs to minimize the risk of tumor recurrence in cancer patients.


Cancer stem cell Tumor dormancy Minimal residual disease Disseminated tumor cell Circulating tumor cell Metastasis Tumor initiation Tumorigenicity Progression Recurrence Relapse Therapy resistance Epidemiology Animal models Antitumor immunity Immune evasion Immunoescape Angiogenesis Angiogenic switch Apoptosis Quiescence