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Insight into Intratumoral Heterogeneity Through Single CTC Sequencing and CDX Analysis

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Circulating Tumor Cells

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Tumors contain a high degree of molecular heterogeneity which is the substrate of therapeutic resistance and is rooted both by genomic instability and by phenotypic plasticity. Hematogenous dissemination of circulating tumor cells (CTCs) is considered as the major form of metastatic spread to distant organs. Genomic and functional characterization of CTCs may provide insight into the biology of cancer cells that promote metastases formation and provide a route to disease progression. As CTCs integrate information from spatially distinct metastatic sites, they may inform intratumoral heterogeneity and therapeutic resistance mechanisms. Here, we show how CTC analyses at the single-cell level may provide important information regarding intratumoral heterogeneity and potential therapeutic resistance mechanisms in ALK-positive non-small-cell lung cancer (NSCLC). We also present the phenotypical and genetic characterization of a neuroendocrine trans-differentiation castration-resistant prostate cancer (CRPC) CTC-derived xenograft (CDX) model. This CDX model represents a unique tool to improve our understanding of lineage plasticity and genetic mechanisms driving therapeutic resistance in CRPC.

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Acknowledgments

The authors are grateful to the patients and their families. The authors thank Pr. Jean-Yves Scoazec for critical insights and discussions, Virginie Marty for expert technical assistance, and Dr. Jean-Gabriel Judde, Dr. Stefano Cairo, Dr. Olivier Deas, and Laura Brulle-Soumare for expert support in CDX development and fruitful collaboration. They also thank Menarini Silicon Biostems particularly Nicolò Manaresi to provide us the Ampli1 Cancer Hotspot Panel Custom Beta, and Genny Buson, Marianna Garonzi, and Claudio Forcato for their help in generating and analyzing the Ampli1 LowPass data.

Funding

This work was supported by the Agence nationale de la recherche (ANR-CE17- 0006-01) and the Innovative Medicines Initiatives11th call CANCER-ID (IMI-JU-11-2013, grant no. 115749).

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Authors and Affiliations

  1. Gustave Roussy, Université Paris-Saclay, “Rare Circulating Cells” Translational Platform, CNRS UMS3655 - INSERM US23 AMMICA, Villejuif, France

    Marianne Oulhen, Tala Tayoun, Agathe Aberlenc, Patrycja Pawlikowska & Françoise Farace

  2. INSERM, U981 “Identification of Molecular Predictors and New Targets for Cancer Treatment”, Villejuif, France

    Marianne Oulhen, Tala Tayoun, Agathe Aberlenc, Patrycja Pawlikowska & Françoise Farace

  3. Univ Paris Sud, Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicetre, France

    Tala Tayoun & Françoise Farace

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  1. Marianne Oulhen
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  4. Patrycja Pawlikowska
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  5. Françoise Farace
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Correspondence to Françoise Farace .

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  1. Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA

    Richard J. Cote

  2. ACTC Lab, Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece

    Evi Lianidou

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Oulhen, M., Tayoun, T., Aberlenc, A., Pawlikowska, P., Farace, F. (2023). Insight into Intratumoral Heterogeneity Through Single CTC Sequencing and CDX Analysis. In: Cote, R.J., Lianidou, E. (eds) Circulating Tumor Cells. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-031-22903-9_12

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