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      ctDNA and CTCs in Liquid Biopsy – Current Status and Where We Need to Progress

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          Abstract

          We discuss the current status of liquid biopsy and its advantages and challenges with a focus on pre-analytical sample handling, technologies and workflows. The potential of circulating tumor cells and circulating tumor DNA is pointed out and an overview of corresponding technologies is given.

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          Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.

          Johann de Bono, Howard Scher, R. Montgomery … (2008)
          A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points. Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups ( or =5 CTC/7.5mL). Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P 26 to 9.3 months). CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.
          Article 0 comments Cited 709 times – based on 0 reviews     Review now
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            Circulating tumor cells: liquid biopsy of cancer.

            Catherine Alix-Panabières, Klaus Pantel (2013)
            The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with >400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients. This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular-characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial-mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). A considerable number of promising CTC-detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice. © 2012 American Association for Clinical Chemistry
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              Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling

              Aadel Chaudhuri, Jacob Chabon, Alexander Lovejoy … (2017)
              Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here, we apply cancer personalized profi ling by deep sequencing (CAPP-seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I–III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the fi rst posttreatment blood sample, indicating reliable identifi cation of MRD. Posttreatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months, and 53% of patients harbored ctDNA mutation profi les associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in patients with lung cancer can be accurately detected using CAPP-seq and may allow personalized adjuvant treatment while disease burden is lowest.
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                Author and article information

                Contributors
                Thomas Schlange
                Journal
                Journal ID (nlm-ta): Comput Struct Biotechnol J
                Journal ID (iso-abbrev): Comput Struct Biotechnol J
                Title: Computational and Structural Biotechnology Journal
                Publisher: Research Network of Computational and Structural Biotechnology
                ISSN (Electronic): 2001-0370
                Publication date PMC-release: 01 June 2018
                Publication date Collection: 2018
                Publication date (Electronic): 01 June 2018
                Volume: 16
                Pages: 190-195
                Affiliations
                [a ]Bayer AG, Pharmaceutical Division, Biomarker Research, Wuppertal, Germany
                [b ]Bayer AG, Pharmaceutical Division, Translational Assay Technology, Berlin, Germany
                Author notes
                [* ]Corresponding author at: Bayer AG, Research Center Elberfeld, Biomarker Research, Bldg. 500, R. 211, Aprather Weg 18a, 42096 Wuppertal, Germany. thomas.schlange@ 123456bayer.de
                Article
                Publisher ID: S2001-0370(18)30006-0
                DOI: 10.1016/j.csbj.2018.05.002
                PMC ID: 6024152
                PubMed ID: 29977481
                SO-VID: 4c43b174-0d83-4599-812c-f6a0ca5a37da
                Copyright © © 2018 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 30 January 2018
                Date revision received : 18 May 2018
                Date accepted : 21 May 2018
                Categories
                Subject: Review Article

                Keywords: liquid biopsy,circulating tumor dna,circulating tumor cells,pre-analytical handling,technology overview
                Data availability:
                Keywords: liquid biopsy, circulating tumor dna, circulating tumor cells, pre-analytical handling, technology overview

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