Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability
Circulating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/337 |
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| author | Tala Tayoun Marianne Oulhen Agathe Aberlenc Françoise Farace Patrycja Pawlikowska |
| author_facet | Tala Tayoun Marianne Oulhen Agathe Aberlenc Françoise Farace Patrycja Pawlikowska |
| author_sort | Tala Tayoun |
| collection | DOAJ |
| description | Circulating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single-cell analytical processes. Indeed, CTC monitoring through molecular and functional characterization may provide an understanding of genomic instability (GI) molecular mechanisms, which contribute to tumor evolution and emergence of resistant clones. In this review, we discuss the sources and consequences of GI seen through single-cell analysis of CTCs in different types of tumors. We present a detailed overview of chromosomal instability (CIN) in CTCs assessed by fluorescence in situ hybridization (FISH), and we reveal utility of CTC single-cell sequencing in identifying copy number alterations (CNA) oncogenic drivers. We highlight the role of CIN in CTC-driven metastatic progression and acquired resistance, and we comment on the technical obstacles and challenges encountered during single CTC analysis. We focus on the DNA damage response and depict DNA-repair-related dynamic biomarkers reported to date in CTCs and their role in predicting response to genotoxic treatment. In summary, the suggested relationship between genomic aberrations in CTCs and prognosis strongly supports the potential utility of GI monitoring in CTCs in clinical risk assessment and therapeutic choice. |
| first_indexed | 2024-03-09T05:28:59Z |
| format | Article |
| id | doaj.art-12064c19e7e44ec1a4ef9f083f441c1d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:28:59Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-12064c19e7e44ec1a4ef9f083f441c1d2023-12-03T12:34:14ZengMDPI AGCells2073-44092021-02-0110233710.3390/cells10020337Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic InstabilityTala Tayoun0Marianne Oulhen1Agathe Aberlenc2Françoise Farace3Patrycja Pawlikowska4Gustave Roussy, Université Paris-Saclay, “Circulating Tumor Cells” Translational Platform, CNRS UMS3655–INSERM US23AMMICA, F-94805 Villejuif, FranceGustave Roussy, Université Paris-Saclay, “Circulating Tumor Cells” Translational Platform, CNRS UMS3655–INSERM US23AMMICA, F-94805 Villejuif, FranceGustave Roussy, Université Paris-Saclay, “Circulating Tumor Cells” Translational Platform, CNRS UMS3655–INSERM US23AMMICA, F-94805 Villejuif, FranceGustave Roussy, Université Paris-Saclay, “Circulating Tumor Cells” Translational Platform, CNRS UMS3655–INSERM US23AMMICA, F-94805 Villejuif, FranceGustave Roussy, INSERM, U981 “Molecular Predictors and New Targets in Oncology”, F-94805 Villejuif, FranceCirculating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single-cell analytical processes. Indeed, CTC monitoring through molecular and functional characterization may provide an understanding of genomic instability (GI) molecular mechanisms, which contribute to tumor evolution and emergence of resistant clones. In this review, we discuss the sources and consequences of GI seen through single-cell analysis of CTCs in different types of tumors. We present a detailed overview of chromosomal instability (CIN) in CTCs assessed by fluorescence in situ hybridization (FISH), and we reveal utility of CTC single-cell sequencing in identifying copy number alterations (CNA) oncogenic drivers. We highlight the role of CIN in CTC-driven metastatic progression and acquired resistance, and we comment on the technical obstacles and challenges encountered during single CTC analysis. We focus on the DNA damage response and depict DNA-repair-related dynamic biomarkers reported to date in CTCs and their role in predicting response to genotoxic treatment. In summary, the suggested relationship between genomic aberrations in CTCs and prognosis strongly supports the potential utility of GI monitoring in CTCs in clinical risk assessment and therapeutic choice.https://www.mdpi.com/2073-4409/10/2/337circulating tumor cellsgenomic instabilitychromosomal instabilityDNA-repairtumor genetic heterogeneity |
| spellingShingle | Tala Tayoun Marianne Oulhen Agathe Aberlenc Françoise Farace Patrycja Pawlikowska Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability Cells circulating tumor cells genomic instability chromosomal instability DNA-repair tumor genetic heterogeneity |
| title | Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability |
| title_full | Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability |
| title_fullStr | Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability |
| title_full_unstemmed | Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability |
| title_short | Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability |
| title_sort | tumor evolution and therapeutic choice seen through a prism of circulating tumor cell genomic instability |
| topic | circulating tumor cells genomic instability chromosomal instability DNA-repair tumor genetic heterogeneity |
| url | https://www.mdpi.com/2073-4409/10/2/337 |
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