The field of tumour dormancy, originally defined as a clinical phenomenon of late recurrence after a long, apparently disease-free period, has seen significant advances that now allow us to think about monitoring and targeting dormant tumour cells to prevent relapse. In this Viewpoint article, we asked experts to share their views on the steps that are needed to translate dormancy research into the clinic.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Naume, B. et al. Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. J. Clin. Oncol. 32, 3848–3857 (2014).
Hartkopf, A. D. et al. Disseminated tumour cells from the bone marrow of early breast cancer patients: results from an international pooled analysis. Eur. J. Cancer 154, 128–137 (2021).
Borgen, E. et al. NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients. Breast Cancer Res. 20, 120 (2018).
Schlimok, G. et al. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc. Natl Acad. Sci. USA 84, 8672–8676 (1987).
Hu, J. et al. STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma. Nature 616, 806–813 (2023).
Klein, C. A. Cancer progression and the invisible phase of metastatic colonization. Nat. Rev. Cancer 20, 681–694 (2020).
Dalla, E., Sreekumar, A., Aguirre-Ghiso, J. A. & Chodosh, L. A. Dormancy in breast cancer. Cold Spring Harb. Perspect. Med. 4, 183–191 (2023).
Correia, A. L. Locally sourced: site-specific immune barriers to metastasis. Nat. Rev. Immunol. 23, 522–538 (2023).
Correia, A. L. et al. Hepatic stellate cells suppress NK cell sustained breast cancer dormancy. Nature 600, E7 (2021).
Lim, A. R. & Ghajar, C. M. Thorny ground, rocky soil: tissue-specific mechanisms of tumor dormancy and relapse. Semin. Cancer Biol. 78, 104–123 (2022).
Hadfield, G. The dormant cancer cell. Br. Med. J. 2, 607–610 (1954).
Klein, C. A. Framework models of tumor dormancy from patient-derived observations. Curr. Opin. Genet. Dev. 21, 42–49 (2011).
Pommier, A. et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases. Science 4908, eaao4908 (2018).
Baldominos, P. et al. Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche. Cell 185, 1694–1708 (2022).
Boyd, A. L. et al. Identification of chemotherapy-induced leukemic-regenerating cells reveals a transient vulnerability of human AML recurrence. Cancer Cell 34, 483–498.e5 (2018).
Beneyto-Calabuig, S., Ludwig, A. K., Müller-Tidow, C. & Velten, L. Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia. Cell Stem Cell 30, 706–721.e8 (2022).
Duy, C. et al. Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence. Cancer Discov. 11, 1542–1561 (2021).
Farge, T. et al. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov. 7, 716–735 (2017).
Banys, M. et al. Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial. BMC Cancer 13, 480 (2013).
Bayne, L. J. et al. Identifying breast cancer survivors with dormant disseminated tumor cells: the PENN-SURMOUNT Screening Study. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS20-PD9-11 (2021).
Bayne, L. J. et al. Detection and targeting of minimal residual disease in breast cancer to reduce recurrence: the PENN-SURMOUNT and CLEVER trials. Cancer Res. abstr. https://doi.org/10.1158/1538-7445.SABCS17-OT2-07-09 (2018).
Acknowledgements
J.A. is supported by the Ludwig Center at Harvard, the Ira Schneider Foundation, the Parker Institute for Immunotherapy and the Department of Defense BCMRP Era of Hope Scholar Award W81XWH-22-BCRP-EOHS2. J.A.A-G. is supported by grants from the National Institute of Health/National Cancer Institute (NIH/NCI) (CA109182, CA013330, CA253977), Department of Defense Breast Cancer Research Program (DoD-BCRP), Department of Defense Melanoma Research Program (DoD-MRP), The Mark Foundation, J. Gurwin Foundation and Melanoma Research Alliance and Montefiore Einstein Comprehensive Cancer Center. J.A.A-G is a Samuel Waxman Cancer Research Foundation Investigator, and a member of The Ruth L. and David S. Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine. L.A.C. thanks E. Chislock and A. Sreekumar for the helpful comments, and acknowledges support from the Breast Cancer Research Foundation, NIH, DoD and the Abramson Cancer Center. A.L.C. acknowledges support by the Champalimaud Foundation, the Beug Foundation (2021 Metastasis Research Prize), the European Molecular Biology Organization (EMBO Installation Grant 5329) and the Portuguese Foundation for Science and Technology (FCT ERC-Portugal Grant). C.A.K. acknowledges support from the Deutsche Forschungsgemeinschaft DFG (SFB/TRR 305).
Author information
Authors and Affiliations
Contributions
Judith Agudo: Judith Agudo is an Assistant Professor in the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and the Department of Immunology at Harvard Medical School. She is also a member researcher in both the Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute and the Ludwig Cancer Center at Harvard, and an affiliated member of the Harvard Stem Cell Institute and a New York Stem Cell Foundation–Robertson Investigator. The Agudo laboratory investigates mechanisms of immune evasion of cancer stem cells and quiescent cancer cells with the goal of identifying immune-based strategies to prevent metastasis.
Julio A. Aguirre-Ghiso: Julio A. Aguirre-Ghiso is the Rose Falkenstein Chair in Cancer Research, Professor of Cell Biology and Director of the Cancer Dormancy & Tumor Microenvironment Institute at Albert Einstein College of Medicine. His work led a paradigm shift, revealing novel cancer biology that diverges from the notion that cancer is perpetually proliferating. His team discovered that reciprocal crosstalk between disseminated tumour cells and the microenvironment regulates the inter-conversion between dormancy and metastasis initiation. His laboratory also provided a mechanistic understanding of the process of early dissemination and revealed how it contributes to dormancy and metastatic progression and how stress-adaptive pathways allow cancer cells to persist while quiescent.
Mickie Bhatia: Mickie Bhatia is a Professor at McMaster University, the Canada Research Chair in Human Stem Cell Biology, the Michael DeGroote Chair of Human Stem Cell Biology and Cancer Research and currently the Program Director of Experimental Therapeutics in human leukaemias. His program is integrated with several clinical sites and forms the hub for chemical genomics and drug discovery targeting putative cancer cells with stem cell properties. His laboratory was the first to culture pluripotent stem cell in Canada and leverages stem cell technologies and novel assay development for preclinical and translational phase I study in patients.
Lewis A. Chodosh: Lewis A. Chodosh is Perelman Professor and Chair of the Department of Cancer Biology at the Perelman School of Medicine at the University of Pennsylvania, Associate Director for Basic Science at the Abramson Cancer Center and, along with Angela DeMichele, co-founder and co-director of the 2-PREVENT Translational Center of Excellence, which is focused on developing novel approaches to prevent tumour recurrence in patients with breast cancer by targeting dormant minimal residual disease. His laboratory focuses on understanding mechanisms of tumour dormancy and recurrence, developing improved methods for detecting and characterizing disseminated tumour cells in patients, and leveraging those advances through clinical trials. He has been elected to the National Academy of Medicine, Association of American Physicians and American Society for Clinical Investigation.
Ana Luísa Correia: Ana Luísa Correia leads the Cancer Dormancy & Immunity Lab at the Champalimaud Foundation. Her group strives to understand what makes a tissue favourable or not to metastasis and leverages this biology into therapeutic interventions that reliably prevent the emergence of metastases in patients with cancer. Ana has received a few international awards (2021 Metastasis Research Prize, 2022 Pfizer Oncology and AACR 2022 NextGen Stars) and is an EMBO Young Investigator.
Christoph A. Klein: Christoph A. Klein studied Medicine at the Ludwig-MaximiliansUniversity in Munich. He is heading two laboratories, one at the University of Regensburg for basic metastasis research and one at the Fraunhofer Society for clinical translation of the results. The major focus of the said laboratories is on the earliest beginnings and mechanisms of metastatic spread and colonization.
Corresponding authors
Ethics declarations
Competing interests
J.A. and A.L.C. declare no competing interests. J.A.A-G. is a scientific co-founder of, scientific advisory board member and equity owner in HiberCell and receives financial compensation as a consultant for HiberCell, a Mount Sinai spin-off company focused on therapeutics that prevent or delay cancer recurrence. M.B. declares no competing interests L.A.C. has served as an expert consultant to Teva Pharmaceuticals, Eisai, Sanofi, Eli Lilly, Whittaker, Clark and Daniels, Wyeth, Imerys, Colgate, Becton Dickinson, Sterigenics and the US Department of Justice in litigation. Patent applicant: University of Pennsylvania. Inventors: Lewis Chodosh, Elizabeth Chislock. Patent application 16/620,580. Status: Pending. Aspect of manuscript covered: DTC detection in bone marrow aspirates. C.A.K. is a scientific advisory board member of HiberCell, New York.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Agudo, J., Aguirre-Ghiso, J.A., Bhatia, M. et al. Targeting cancer cell dormancy. Nat Rev Cancer 24, 97–104 (2024). https://doi.org/10.1038/s41568-023-00642-x
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41568-023-00642-x
This article is cited by
-
Finding the needle in the haystack
Nature Reviews Cancer (2024)
