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The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: from Enumeration to Molecular Characterization.

ABSTRACT: Circulating Tumor cells (CTCs) represent tumor cells in the blood stream dislodged from the primary tumor. The presence of CTCs in the bloodstream provides a unique opportunity to sample cancer tissue by means of a relatively less-invasive "liquid biopsy." Over the past decade, there has been a tremendous increase in the amount of research examining the potential clinical utility of CTCs in the management of cancer. A number of techniques to refine the sensitivity and range of CTC assays are also in development. In this article, we review the recent developments in the current and potential clinical applications of CTCs in breast cancer. CTC enumeration already has an established role as a prognostic biomarker in metastatic breast cancer, while molecular characterization of CTCs can serve as a potential predictive biomarker for therapy selection, pharmacodynamic evaluation, and identification of novel actionable targets for novel therapies. The role of CTCs in breast cancer screening and detection of recurrence is currently limited. Further development in techniques will be pivotal in enhancing the broad applicability of CTCs and advancing the field of personalized breast cancer therapy.

SUBMITTER: Sarangi S

PROVIDER: S-EPMC4242094 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: from Enumeration to Molecular Characterization.

Sarangi Sasmit S Mosulpuria Kailash K Higgins Michaela J MJ Bardia Aditya A

Current breast cancer reports 20140901 3

Circulating Tumor cells (CTCs) represent tumor cells in the blood stream dislodged from the primary tumor. The presence of CTCs in the bloodstream provides a unique opportunity to sample cancer tissue by means of a relatively less-invasive "liquid biopsy." Over the past decade, there has been a tremendous increase in the amount of research examining the potential clinical utility of CTCs in the management of cancer. A number of techniques to refine the sensitivity and range of CTC assays are als ...[more]

PMID: 25431637

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Project description:IntroductionThere is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring.Materials and methodsCTCs isolation was carried out in peripheral blood samples from 29 mCRPC patients that undergo systemic chemotherapy based on taxanes (docetaxel/cabazitaxel) and 19 healthy controls using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize the CTC population. A panel of 17 genes related with prostate biology, hormone regulation, stem properties, tumor aggressiveness and taxanes responsiveness was analysed to identify an expression signature characterizing the CTCs.ResultsPatients with ? 5 CTCs/7.5ml of peripheral blood at baseline and during the treatment showed lower progression free survival (PFS) and overall survival (OS). Changes of CTCs levels during the treatment were also associated with the patient's outcome. These results confirmed previous data obtained using CellSearch in mCRPC. In addition, we found a CTC profile mainly characterized by the expression of relevant genes for the hormone dependent regulation of PCa such as AR and CYP19 together with genes strongly implicated in PCa progression and resistance development such as BIRC5, TUB1A, GDF15, RAB7 and SPINK1. Our gene-expression profiling also permitted the identification of valuable prognostic biomarkers. Thus, high levels of AR, CYP19 and GDF15 were associated with poor PFS rates while AR, GDF15 and BIRC5 were also found as reliable predictors of OS. Besides, a logistic model using KLK3 and BIRC5 showed a high specificity and sensitivity compared to CellSearch to discriminate patients with a more aggressive evolution.ConclusionsThe molecular characterization of CTCs from advanced mCRPC patients provided with a panel of specific biomarkers, including genes related to taxanes resistance, with a promising applicability as "liquid biopsy" for the management of these patients.

Dataset Information

The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: from Enumeration to Molecular Characterization.

Publications

The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: from Enumeration to Molecular Characterization.

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