How much do we know about the metastatic process? - Brief review on detecting disseminated cancer cells

Sep 21, 2026

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Cancer cells disseminate from primary sites to distant organs, where disseminated cancer cells (DCCs) can persist even before overt, symptomatic progression. Experimental models and clinical samples show DCCs can enter a nonproliferative cellular dormancy state and reactivate in response to niche-derived signals. Clinical detection in lymph nodes or bone marrow correlates with poor survival. Current therapies mainly target primary-tumor biology and do not eliminate dormant DCC populations, allowing ongoing metastatic waves.

LanguageEnglish

CategoryHealthcare

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Pages37

Reading Time1 h 33 min

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Abstract

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Introduction

Author Manuscript Author Manuscript Author Manuscript Author Manuscript | | HHS Public Access
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Clin Exp Metastasis. Author manuscript; available in PMC 2024 September 05. | | --- | --- | Published in final edited form as: Clin Exp Metastasis. 2024 August ; 41(4): 275–299. doi:10.1007/s10585-023-10248-0 . How much do we know about the metastatic process? Carolina Rodriguez-Tirado 1,2,3,4,5 , Maria Soledad Sosa 1,2,3,4,5 1 Department of Microbiology and Immunology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA 2 Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA 3Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine/ Montefiore Medical Center, Bronx, NY 10461, USA 4Cancer Dormancy and Tumor Microenvironment Institute/Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA 5 Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA Abstract Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the early and asymptomatic stages of tumor progression. In experimental models and clinical samples, DCCs can be detected in a nonproliferative state, defined as cellular dormancy. This state can persist for extended periods until DCCs reawaken, usually in response to niche-derived reactivation signals. Therefore, their clinical detection in sites like lymph nodes and bone marrow is linked to poor survival. Current cancer therapy designs are based on the biology of the primary tumor and do not target the biology of the dormant DCC population and thus fail to eradicate the initial or subsequent waves of metastasis. In this brief review, we discuss the current methods for detecting DCCs and highlight new strategies that aim to target DCCs that constitute minimal residual disease to reduce or prevent metastasis formation. Furthermore, we present current evidence on the relevance of DCCs derived from early stages of tumor progression in metastatic disease and describe the animal models available for their study. We also discuss our current understanding of the dissemination mechanisms utilized by genetically less-and more-advanced cancer cells, which include the functional analysis of Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/) . ✉ Carolina Rodriguez-Tirado, [carolina.rodriguez@einsteinmed.edu](carolina.rodriguez@einsteinmed.edu), Maria Soledad Sosa, [maria.sosa@einsteinmed.edu](maria.sosa@einsteinmed.edu). Author contributions CRT and MSS wrote the manuscript and prepared figures. All authors reviewed the manuscript. Competing interests The authors declare no competing interests. Presented at the 9th International Congress on Cancer Metastasis through the Lymphovascular System, May 4–6, 2023, in San Francisco, CA. To be published in a Special Issue of Clinical and Experimental M

FAQs

What are disseminated cancer cells (DCCs) and where can they be found?

DCCs are cancer cells that leave primary sites and travel through circulation to distant tissues, where they lodge even during early, asymptomatic tumor progression. They can be detected in sites such as lymph nodes and bone marrow.

How does cellular dormancy influence metastatic progression?

After DCCs lodge at distant sites, they can remain undetected for years or decades by entering a cellular dormancy state. They can later reawaken, often triggered by niche-derived reactivation signals.

Why do current cancer therapies often fail to eradicate metastasis?

Many therapies are designed around the biology of the primary tumor and do not target the biology of dormant DCCs. As a result, initial or subsequent waves of metastasis may not be fully eradicated.

Sep 21, 2026

Upload by Levi