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  • Review Article
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Clinical opportunities and challenges in targeting tumour dormancy

Nature Reviews Clinical Oncology volume 10, pages 41–51 (2013)Cite this article

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Abstract

The reactivation of cancer cells following a seemingly successful treatment of the primary tumour with initial therapies (such as tumour excision or systemic therapy) is a well-known phenomenon. This metastatic rebirth is preceded by an interlude, termed dormancy, when cancer sleeps undetected for periods that can last years or even decades. Discoveries over the past 10 years have revealed the therapeutic potential of prolonging dormancy for maintaining a clinically asymptomatic state, or the permanent clearance of dormant residual disseminated cancer cells to affect a 'cure'. Here, we provide an overview of the mechanisms of dormancy and use genitourinary cancers as models to demonstrate how dormancy principles could be exploited clinically. Data from these models have yielded promising therapeutic strategies to address dormancy as well as diagnostics that could enable clinicians to monitor the dormant state of cancer in patients. This Review also aims to convey that dormancy, as a whole, likely results from coalescing contributions made by each of the three types of dormancy discussed (cellular, angiogenic and immunological). In our opinion, dormancy-directed therapies will prove most effective when the effect of these cumulative contributions are understood and targeted.

Key Points

  • Although the concept of cancer dormancy has been considered for over 120 years, it has been largely overlooked as a regulator of disease progression until the past two decades

  • Cancer dormancy can be currently explained by three mechanisms (cellular, angiogenic and immunological), with each making important contributions to the dormant state as a whole

  • Preclinical studies are providing an understanding of dormancy leading to therapeutic strategies to maintain or induce dormancy, or alternatively clear residual dormant cells from patients in remission to affect a permanent cure

  • New immunotherapies and antiangiogenic agents have been approved in the past decade and these may provide new tools to test the proposed mechanisms of dormancy in the clinical setting

  • Technological advances are emerging that might enable safe, effective and low-cost, long-term monitoring of dormancy required for clinical assessment of dormancy, and the evaluation of therapeutic efficacy in future clinical trials

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Figure 1: Interrelated mechanisms of dormancy.

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Acknowledgements

This work is supported by National Institutes of Health grants CA075115 and CA104106 to DT. The authors would like to thank Dan Welch for his critical review of the manuscript and contribution of unpublished data.

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  1. Department of Surgery and Pharmacology, University of Colorado Comprehensive Cancer Center, Building 500, 13001 East 17th Place, Aurora, 80045, CO, USA

    Jonathan A. Hensel & Dan Theodorescu

  2. Department of Medicine, University of Colorado Comprehensive Cancer Center, Building 500, 13001 East 17th Place, Aurora, 80045, CO, USA

    Thomas W. Flaig

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J. A. Hensel and T. W. Flaig researched data for the article, substantially contributed to the discussion of content and wrote the article. D. Theodorescu reviewed and edited the manuscript prior to submission.

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Hensel, J., Flaig, T. & Theodorescu, D. Clinical opportunities and challenges in targeting tumour dormancy. Nat Rev Clin Oncol 10, 41–51 (2013). https://doi.org/10.1038/nrclinonc.2012.207

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