Special Issue "Liquid Biopsy in Solid Tumor Oncology"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 January 2020).

Special Issue Editor

Prof. Dr. Jens Höppner
Website
Guest Editor
1. Comprehensive Cancer Center Freiburg, Medical Center—University of Freiburg, Freiburg, Germany
2. Department of General and Visceral Surgery, Medical Center—University of Freiburg, Freiburg, Germany
Interests: gastrointestinal oncology; minimal invasive surgery; liquid biopsy

Special Issue Information

Dear Colleagues,

“Liquid biopsy” comprises techniques in cancer diagnosis that are faster, easier, and less risky and much more comfortable for the patient than classical invasive biopsies. “Liquid biopsies” represent a paradigm shift in the treatment of patients with solid cancers. The possibility to perform repeated tumor sampling and real-time monitoring of tumor disease progression and treatment response enables early intervention and personalized treatment of the patient. The possibilities of, and the prospects of success for, these emerging technologies are steeply increasing in solid tumor disease. Detection and analysis of circulating tumor cells, free DNA, RNA, or exosomes are innovative and non-intrusive ways to perform diagnosis and/or follow-up. In this Special Issue, we aim to cover all aspects of liquid biopsy in solid tumor disease research. We welcome articles on the discovery, validation, and clinical application of the different techniques and methods of liquid biopsy.

Prof. Dr. Jens Höppner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Liquid biopsy
  • Cancer diagnosis
  • Solid cancer/tumor
  • Circulating tumor cells
  • Free DNA
  • RNA
  • Exosomes

Published Papers (5 papers)

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Research

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Open AccessArticle
Personalized Treatment Selection and Disease Monitoring Using Circulating Tumor DNA Profiling in Real-World Cancer Patient Management
Diagnostics 2020, 10(8), 550; https://doi.org/10.3390/diagnostics10080550 - 02 Aug 2020
Abstract
Background: Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust [...] Read more.
Background: Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at relatively low costs. Yet, their value for ctDNA-based management of a broad population of cancer patients beyond clinical trials remains elusive. Methods: We developed mutation-specific ddPCR assays that were optimized for their use in real-world cancer management, covering 12 genetic aberrations in common cancer genes, such as EGFR, BRAF, KIT, KRAS, and NRAS. We assessed the limit of detection (LOD) and the limit of blank (LOB) for each assay and validated their performance for ctDNA detection using matched tumor sequencing. Results: We applied our custom ddPCR assays to 352 plasma samples from 96 patients with solid tumors. Mutation detection in plasma was highly concordant with tumor sequencing, demonstrating high sensitivity and specificity across all assays. In 20 cases, radiographic cancer progression was mirrored by an increase of ctDNA concentrations or the occurrence of novel mutations in plasma. Moreover, ctDNA profiling at diagnosis and during disease progression reflected personalized treatment selection through the identification of actionable gene targets in 20 cases. Conclusion: Collectively, our work highlights the potential of ctDNA assessment by sensitive ddPCR for accurate disease monitoring, robust identification of resistance mutations, and upfront treatment selection in patients with solid tumors. We envision an increasing future role for ctDNA profiling within personalized cancer management in daily clinical routine. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumor Oncology)
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Open AccessArticle
Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer
Diagnostics 2020, 10(5), 305; https://doi.org/10.3390/diagnostics10050305 - 15 May 2020
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of death from cancer. Circulating tumor cells (CTCs) with stem-like characteristics lead to distant metastases and thus contribute to the dismal prognosis of PDAC. Our purpose is to investigate the role of stemness [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of death from cancer. Circulating tumor cells (CTCs) with stem-like characteristics lead to distant metastases and thus contribute to the dismal prognosis of PDAC. Our purpose is to investigate the role of stemness in CTCs derived from a genetically engineered mouse model of PDAC and to further explore the potential molecular mechanisms. The publically available RNA sequencing dataset GSE51372 was analyzed, and CTCs with (CTC-S) or without (CTC-N) stem-like features were discriminated based on a principal component analysis (PCA). Differentially expressed genes, weighted gene co-expression network analysis (WGCNA), and further functional enrichment analyses were performed. The prognostic role of the candidate gene (CTNNB1) was assessed in a clinical PDAC patient cohort. Overexpression of the pluripotency marker Klf4 (Krüppel-like factor 4) in CTC-S cells positively correlates with Ctnnb1 (β-Catenin) expression, and their interaction presumably happens via protein–protein binding in the nucleus. As a result, the adherens junction pathway is significantly enriched in CTC-S. Furthermore, the overexpression of Ctnnb1 is a negative prognostic factor for progression-free survival (PFS) and relapse-free survival (RFS) in human PDAC cohort. Overexpression of Ctnnb1 may thus promote the metastatic capabilities of CTCs with stem-like properties via adherens junctions in murine PDAC. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumor Oncology)
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Open AccessArticle
Development of a Highly Sensitive Technique for Capturing Renal Cell Cancer Circulating Tumor Cells
Diagnostics 2019, 9(3), 96; https://doi.org/10.3390/diagnostics9030096 - 14 Aug 2019
Cited by 4
Abstract
purpose: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy [...] Read more.
purpose: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy is less invasive than conventional tissue biopsy is, enabling frequent biopsies and, therefore, is considered effective for monitoring the treatment course. Circulating tumor cells (CTCs) are a representative liquid biopsy specimen. In the present study, we focused on developing our novel technology for capturing renal cell cancer (RCC)-CTCs using an anti-G250 antibody combined with new devices. Basic experiments of our technology showed that it was possible to detect RCC-CTC with a fairly high accuracy of about 95%. Also, RCC-CTC was identified in the peripheral blood of actual RCC patients. Additionally, during the treatment course of the RCC patient, change in the number of RCC-CTC was confirmed in one case. We believe that the technology we developed will be useful for determining the treatment efficacy and drug selection for the treatment of renal cell cancer (RCC). In order to solve issues such as thresholds setting of this technology, large-scale clinical trials are expected. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumor Oncology)
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Review

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Open AccessReview
Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer’s Biomarkers
Diagnostics 2020, 10(4), 215; https://doi.org/10.3390/diagnostics10040215 - 13 Apr 2020
Cited by 7
Abstract
In recent years, there has been an increase in knowledge of cancer, accompanied by a technological development that gives rise to medical oncology. An instrument that allows the implementation of individualized therapeutic strategies is the liquid biopsy. Currently, it is the most innovative [...] Read more.
In recent years, there has been an increase in knowledge of cancer, accompanied by a technological development that gives rise to medical oncology. An instrument that allows the implementation of individualized therapeutic strategies is the liquid biopsy. Currently, it is the most innovative methodology in medical oncology. Its high potential as a tool for screening and early detection, the possibility of assessing the patient’s condition after diagnosis and relapse, as well as the effectiveness of real-time treatments in different types of cancer. Liquid biopsy is capable of overcoming the limitations of tissue biopsies. The elements that compose the liquid biopsy are circulating tumor cells, circulating tumor nucleic acids, free of cells or contained in exosomes, microvesicle and platelets. Liquid biopsy studies are performed on various biofluids extracted in a non-invasive way, and they can be performed both from the blood and in urine, saliva or cerebrospinal fluid. The development of genotyping techniques, using the elements that make up liquid biopsy, make it possible to detect mutations, intertumoral and intratumoral heterogeneity, and provide molecular information on cancer for application in medical oncology in an individualized way in different types of tumors. Therefore, liquid biopsy has the potential to change the way medical oncology could predict the course of the disease. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumor Oncology)
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Open AccessReview
Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas
Diagnostics 2020, 10(4), 192; https://doi.org/10.3390/diagnostics10040192 - 30 Mar 2020
Abstract
The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research [...] Read more.
The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumor Oncology)
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