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Metastasis Prevention: Focus on Metastatic Circulating Tumor Cells

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Abstract

Metastasis is the main cause of cancer death. Metastatic foci are derived from tumor cells that detach from the primary tumor and then enter the circulation. Circulating tumor cells (CTCs) are generally associated with a high probability of distant metastasis and a negative prognosis. Most CTCs die in the bloodstream, and only a few cells form metastases. Such metastatic CTCs have a stem-like and hybrid epithelial-mesenchymal phenotype, can avoid immune surveillance, and show increased therapy resistance. Targeting metastatic CTCs and their progenitors in primary tumors and their descendants, particularly disseminated tumor cells, represents an attractive strategy for metastasis prevention. However, current therapeutic strategies mainly target the primary tumor and only indirectly affect metastasis-initiating cells. Here, we consider potential methods for preventing metastasis based on targeting molecular and cellular features of metastatic CTCs, including CTC clusters. Also, we emphasize current knowledge gaps in CTC biology that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

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Acknowledgements

We thank Ms. Ekaterina Khitrinskaya for the preparation of the figure.

Author information

Authors and Affiliations

  1. Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634009, Russia

    Maxim E. Menyailo, Ustinia A. Bokova, Anna A. Khozyainova & Evgeny V. Denisov

  2. Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634009, Russia

    Elena E. Ivanyuk

Authors
  1. Maxim E. Menyailo
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  2. Ustinia A. Bokova
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  3. Elena E. Ivanyuk
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  4. Anna A. Khozyainova
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  5. Evgeny V. Denisov
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Corresponding author

Correspondence to Evgeny V. Denisov.

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Funding

This study was supported by the Russian Science Foundation (grant #19-75-30016).

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The authors declare no conflicts of interest.

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All authors drafted and critically revised the manuscript.

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Menyailo, M.E., Bokova, U.A., Ivanyuk, E.E. et al. Metastasis Prevention: Focus on Metastatic Circulating Tumor Cells. Mol Diagn Ther 25, 549–562 (2021). https://doi.org/10.1007/s40291-021-00543-5

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  • DOI: https://doi.org/10.1007/s40291-021-00543-5

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