scholarly journals The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

2021 ◽  
Vol 10 (4) ◽  
pp. 684
Author(s):  
Lorena Alexandra Lisencu ◽  
Eduard-Alexandru Bonci ◽  
Alexandru Irimie ◽  
Ovidiu Balacescu ◽  
Cosmin Lisencu

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.

2017 ◽  
Vol 63 (10) ◽  
pp. 1585-1593 ◽  
Author(s):  
Maren Bredemeier ◽  
Philippos Edimiris ◽  
Pawel Mach ◽  
Mikael Kubista ◽  
Robert Sjöback ◽  
...  

Abstract BACKGROUND Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC− patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC−. CONCLUSIONS ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.


2021 ◽  
Author(s):  
Lorena Alexandra ◽  
Lisencu Cosmin ◽  
Lisencu Eduard-Alexandru ◽  
Bonci Alexandru ◽  
Irimie Ovidiu Balacescu

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