The dormant cancer cell life cycle

Abstract

The success of targeted therapies and immunotherapies has created optimism that cancers may be curable. However, not all patients respond, drug resistance is common and many patients relapse owing to dormant cancer cells. These rare and elusive cells can disseminate early and hide in specialized niches in distant organs before being reactivated to cause disease relapse after successful treatment of the primary tumour. Despite their importance, we are yet to leverage knowledge generated from experimental models and translate the potential of targeting dormant cancer cells to prevent disease relapse in the clinic. This is due, at least in part, to the lack of adherence to consensus definitions by researchers, limited models that faithfully recapitulate this stage of metastatic spread and an absence of interdisciplinary approaches. However, the application of new high-resolution, single-cell technologies is starting to revolutionize the field and transcend classical reductionist models of studying individual cell types or genes in isolation to provide a global view of the complex underlying cellular ecosystem and transcriptional landscape that controls dormancy. In this Perspective, we synthesize some of these recent advances to describe the hallmarks of cancer cell dormancy and how the dormant cancer cell life cycle offers opportunities to target not only the cancer but also its environment to achieve a durable cure for seemingly incurable cancers.

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Fig. 1: Brief history of cancer cell dormancy.
Fig. 2: Model of cancer cell dormancy.
Fig. 3: Habitats and niches for dormant cancer cells.
Fig. 4: Dormant cancer cell life cycle and the hallmarks of cancer cell dormancy.
Fig. 5: Targeting the dormant cancer cell life cycle.

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Acknowledgements

This work was supported by P. and V. Duncan and the National Health and Medical Research Council (1139237, 1104031 and 1140996), a Kay Stubbs Cancer Research Grant, Cancer Council New South Wales Grant, Prostate Cancer Foundation of Australia and The Movember Foundation. T.G.P. is a National Health and Medical Research Council Senior Research Fellow (1155678). P.I.C. is supported by Mrs J. Gibson and the Ernest Heine Family Foundation.

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Both T.G.P. and P.I.C. researched the data for the article, provided substantial contributions to discussions of the content and contributed equally to writing the article and to reviewing and editing the manuscript before submission.

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Correspondence to Tri Giang Phan or Peter I. Croucher.

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T.G.P. is a consultant of Imugene Pty Ltd. P.I.C. has grant funding and has been on advisory boards and speaker bureaus for Amgen Inc.

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Nature Reviews Cancer thanks J. J. Bravo-Cordero and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Phan, T.G., Croucher, P.I. The dormant cancer cell life cycle. Nat Rev Cancer 20, 398–411 (2020). https://doi.org/10.1038/s41568-020-0263-0

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