Circulating Tumor Cells as a Tool to Untangle the Breast Cancer Heterogeneity Issue

Breast cancer (BC) is a disease characterized by high degrees of heterogeneity at morphologic, genomic, and genetic levels, even within the same tumor mass or among patients. As a consequence, different subpopulations coexist and less represented clones may have a selective advantage, significantly influencing the outcome of BC patients. Circulating tumor cells (CTCs) represent a rare population of cells with a crucial role in metastatic cascade, and in recent years have represented a fascinating alternative to overcome the heterogeneity issue as a “liquid biopsy”. However, besides the raw enumeration of these cells in advanced epithelial tumors, there are no CTC-based assays applied in the clinical practice to improve personalized medicine. In this review, we report the latest findings in the field of CTCs for intra-tumoral heterogeneity unmasking in BC, supporting the need to deepen their analysis to investigate their role in metastatic process and include the molecular characterization in the clinical practice. In the future, CTCs will be helpful in monitoring patients during treatment, as well as to better address therapeutic strategies.

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Abstract P1-01-05: Prognostic values of circulating tumor cells (CTC) and cancer associated macrophage-like cells (CAML) enumerations in metastatic breast cancer: The role for innate immunity in the metastatic process

10.1158/1538-7445.sabcs16-p1-01-05 ◽

2017 ◽

Author(s):

Z Mu ◽

C Wang ◽

Z Ye ◽

G Rossi ◽

L Austin ◽

...

Keyword(s):

Breast Cancer ◽

Innate Immunity ◽

Metastatic Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

Metastatic Process

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Notch and Breast Cancer Metastasis

10.20944/preprints201809.0307.v1 ◽

2018 ◽

Author(s):

Yu Zhang ◽

Huan Deng

Keyword(s):

Breast Cancer ◽

Notch Signaling ◽

Tumor Cells ◽

Cancer Metastasis ◽

Disseminated Tumor Cells ◽

Breast Cancer Metastasis ◽

Therapeutic Strategies ◽

Substantial Evidence ◽

Metastatic Process ◽

Targeted Therapeutic

Metastasis is a major cause factor for breast cancer (BC)-associated mortality. During the metastatic process, disseminated tumor cells (DTCs) detach from the primary sites, and enter the bloodstream and establish the secondary colonies. Recent studies have provided substantial evidence for the importance of Notch signaling in BC metastasis. Therefore, this review focuses on the mechanisms by which Notch contributes to the origin of BC DTCs, increases their motility, regulates their intravasation and extravasation, protects them from host surveillance, and finally facilitates colonization. Identification of the mechanisms underlying Notch-related BC metastasis will lead to the development of novel Notch-targeted therapeutic strategies to reduce metastasis and significantly improve outcomes.

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Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

International Journal of Molecular Sciences ◽

10.3390/ijms21051696 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1696 ◽

Cited By ~ 4

Author(s):

Maxim E. Menyailo ◽

Maria S. Tretyakova ◽

Evgeny V. Denisov

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Potential ◽

Critical Issue ◽

In Vivo Studies ◽

Multistage Process ◽

Metastatic Cascade

Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis.

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