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Cancers
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Liquid Nucleic Acid-Based Biomarkers in Solid Tumors
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Liquid Nucleic Acid-Based Biomarkers in Solid Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 66862

Special Issue Editors

Prof. Nikolas von Bubnoff

E-Mail Website
Guest Editor
Department of Hematology and Oncology, Medical Center, University of Schleswig-Holstein, Campus Lübeck, Germany.
Interests: molecularly based therapies; biomarker development
Dr. Florian Scherer

E-Mail Website
Guest Editor
Department of Hematology, Oncology, and Stem Cell Transplantation, University Medical Center Freiburg, Freiburg, Germany
Interests: noninvasive biomarkers; systems medicine; cancer molecular biology

Special Issue Information

Dear Colleagues,

Tumors release cells, vesicles, proteins and nucleic acid content into circulation. Detection and quantitation of this content in body fluids is called “liquid biopsy” and can inform about the presence of tumor, its activity and dimensions, or the change of genetic or clonal composition over time. The field of Liquid Biopsy has rapidly evolved over the past 10 years. Certain nucleic acid-based diagnostic tests are routinely used to stratify treatments but not for monitoring response to treatment. For metastatic cancers, response to molecularly stratified treatment is short lived, and genetically determined resistance is well characterized. For limited-stage disease, established biomarkers are of limited predictive and prognostic value. Current state-of-the-art techniques allow detection of tumor-derived nucleic acid content with high sensitivity in body fluids and enable monitoring of treatment response, risk stratification and detection of resistant disease clones.

This Special Issue will address prospects of nucleic-acid-based liquid biopsies and focus on conceptual challenges, latest techniques, available data supporting its use as predictive and prognostic biomarkers and possible future integration in routine setting to guide monitoring and sequential treatment decisions in solid tumors.

Prof. Nikolas von Bubnoff
Dr. Florian Scherer
Guest Editors

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 submissions that pass pre-check are 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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
  • circulating tumor (ct)DNA
  • cancer biomarker
  • molecular oncology

Published Papers (16 papers)

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Research

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10 pages, 1073 KiB  
Communication
Circulating Tumor DNA Profiling of a Diffuse Large B Cell Lymphoma Patient with Secondary Acute Myeloid Leukemia
by Irina A. Kerle, Ludwig Jägerhuber, Ramona Secci, Nicole Pfarr, Philipp Blüm, Romina Roesch, Katharina S. Götze, Wilko Weichert, Florian Bassermann, Jürgen Ruland and Christof Winter
Cancers 2022, 14(6), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061371 - 08 Mar 2022
Cited by 3 | Viewed by 2443
Abstract
Diffuse large B cell lymphomas (DLBCL) are the most common neoplasia of the lymphatic system. Circulating cell-free DNA released from tumor cells (ctDNA) has been studied in many tumor entities and successfully used to monitor treatment and follow up. Studies of ctDNA in [...] Read more.
Diffuse large B cell lymphomas (DLBCL) are the most common neoplasia of the lymphatic system. Circulating cell-free DNA released from tumor cells (ctDNA) has been studied in many tumor entities and successfully used to monitor treatment and follow up. Studies of ctDNA in DLBCL so far have mainly focused on tracking mutations in peripheral blood initially detected by next-generation sequencing (NGS) of tumor tissue from one lymphoma manifestation site. This approach, however, cannot capture the mutational heterogeneity of different tumor sites in its entirety. In this case report, we present repetitive targeted next-generation sequencing combined with digital PCR out of peripheral blood of a patient with DLBCL relapse. By combining both detection methods, we were able to detect a new dominant clone of ctDNA correlating with the development of secondary therapy-related acute myeloid leukemia (t-AML) during the course of observation. Conclusively, our case report reinforces the diagnostic importance of ctDNA in DLBCL as well as the importance of repeated ctDNA sequencing combined with focused digital PCR assays to display the dynamic mutational landscape during the clinical course. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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14 pages, 1672 KiB  
Article
Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs
by Elena Tomeva, Olivier J. Switzeny, Clemens Heitzinger, Berit Hippe and Alexander G. Haslberger
Cancers 2022, 14(2), 462; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020462 - 17 Jan 2022
Cited by 17 | Viewed by 6124
Abstract
Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid [...] Read more.
Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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14 pages, 3373 KiB  
Article
Blood-Derived Extracellular Vesicle-Associated miR-3182 Detects Non-Small Cell Lung Cancer Patients
by Kekoolani S. Visan, Richard J. Lobb, Shu Wen Wen, Justin Bedo, Luize G. Lima, Sophie Krumeich, Carlos Palma, Kaltin Ferguson, Ben Green, Colleen Niland, Nicole Cloonan, Peter T. Simpson, Amy E. McCart Reed, Sarah J. Everitt, Michael P. MacManus, Gunter Hartel, Carlos Salomon, Sunil R. Lakhani, David Fielding and Andreas Möller
Cancers 2022, 14(1), 257; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010257 - 05 Jan 2022
Cited by 9 | Viewed by 3329
Abstract
With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, [...] Read more.
With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive sample collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood samples, which could result in earlier therapy and thus improved outcomes and survival for patients. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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14 pages, 12702 KiB  
Article
Stringent Base Specific and Optimization-Free Multiplex Mediator Probe ddPCR for the Quantification of Point Mutations in Circulating Tumor DNA
by Franziska Schlenker, Elena Kipf, Max Deuter, Inga Höffkes, Michael Lehnert, Roland Zengerle, Felix von Stetten, Florian Scherer, Julius Wehrle, Nikolas von Bubnoff, Peter Juelg, Tobias Hutzenlaub and Nadine Borst
Cancers 2021, 13(22), 5742; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225742 - 16 Nov 2021
Cited by 3 | Viewed by 2366
Abstract
There is an increasing demand for optimization-free multiplex assays to rapidly establish comprehensive target panels for cancer monitoring by liquid biopsy. We present the mediator probe (MP) PCR for the quantification of the seven most frequent point mutations and corresponding wild types ( [...] Read more.
There is an increasing demand for optimization-free multiplex assays to rapidly establish comprehensive target panels for cancer monitoring by liquid biopsy. We present the mediator probe (MP) PCR for the quantification of the seven most frequent point mutations and corresponding wild types (KRAS and BRAF) in colorectal carcinoma. Standardized parameters for the digital assay were derived using design of experiments. Without further optimization, the limit of detection (LoD) was determined through spiking experiments with synthetic mutant DNA in human genomic DNA. The limit of blank (LoB) was measured in cfDNA plasma eluates from healthy volunteers. The 2-plex and 4-plex MP ddPCR assays showed a LoB of 0 copies/mL except for 4-plex KRAS G13D (9.82 copies/mL) and 4-plex BRAF V600E (16.29 copies/mL) and allele frequencies of 0.004% ≤ LoD ≤ 0.38% with R2 ≥ 0.98. The quantification of point mutations in patient plasma eluates (18 patients) during follow-up using the 4-plex MP ddPCR showed a comparable performance to the reference assays. The presented multiplex assays need no laborious optimization, as they use the same concentrations and cycling conditions for all targets. This facilitates assay certification, allows a fast and flexible design process, and is thus easily adaptable for individual patient monitoring. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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11 pages, 2686 KiB  
Article
High Cell-Free DNA Integrity Is Associated with Poor Breast Cancer Survival
by Maria Lamminaho, Jouni Kujala, Hanna Peltonen, Maria Tengström, Veli-Matti Kosma and Arto Mannermaa
Cancers 2021, 13(18), 4679; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184679 - 18 Sep 2021
Cited by 7 | Viewed by 3270
Abstract
Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the [...] Read more.
Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker. Methods: We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data. Results: High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS (p = 0.020, hazard ratio (HR) = 1.57, 95% confidence interval (CI) 1.07–2.29, Cox) and BCSS (p = 0.006, HR = 1.93, 95% CI 1.21–3.08)). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance. Conclusions: Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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Review

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22 pages, 2189 KiB  
Review
Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code
by Giuseppe Cammarata, Nadia Barraco, Ilaria Giusti, Valerio Gristina, Vincenza Dolo and Simona Taverna
Cancers 2022, 14(14), 3404; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143404 - 13 Jul 2022
Cited by 12 | Viewed by 3316
Abstract
Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in females worldwide. OC is frequently diagnosed at an advanced stage due to a lack of specific symptoms and effective screening tests, resulting in a poor prognosis for patients. Age, genetic alterations, [...] Read more.
Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in females worldwide. OC is frequently diagnosed at an advanced stage due to a lack of specific symptoms and effective screening tests, resulting in a poor prognosis for patients. Age, genetic alterations, and family history are the major risk factors for OC pathogenesis. Understanding the molecular mechanisms underlying OC progression, identifying new biomarkers for early detection, and discovering potential targets for new drugs are urgent needs. Liquid biopsy (LB), used for cancer detection and management, consists of a minimally invasive approach and practical alternative source to investigate tumor alterations by testing extracellular vesicles (EVs), circulating tumor cells, tumor-educated platelets, and cell-free nucleic acids. EVs are nanosize vesicles shuttling proteins, lipids, and nucleic acids, such as DNA, RNA, and non-coding RNAs (ncRNAs), that can induce phenotypic reprogramming of target cells. EVs are natural intercellular shuttles for ncRNAs, such as microRNAs (miRNAs) and circular-RNAs (circRNAs), known to have regulatory effects in OC. Here we focus on the involvement of circRNAs and miRNAs in OC cancer progression. The circRNA-microRNA-mRNA axis has been investigated with Circbank and miRwalk analysis, unraveling the intricate and detailed regulatory network created by EVs, ncRNAs, and mRNAs in OC. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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27 pages, 1673 KiB  
Review
Circulating Tumor DNA-Based Genomic Profiling Assays in Adult Solid Tumors for Precision Oncology: Recent Advancements and Future Challenges
by Hiu Ting Chan, Yoon Ming Chin and Siew-Kee Low
Cancers 2022, 14(13), 3275; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133275 - 04 Jul 2022
Cited by 11 | Viewed by 3485
Abstract
Genomic profiling using tumor biopsies remains the standard approach for the selection of approved molecular targeted therapies. However, this is often limited by its invasiveness, feasibility, and poor sample quality. Liquid biopsies provide a less invasive approach while capturing a contemporaneous and comprehensive [...] Read more.
Genomic profiling using tumor biopsies remains the standard approach for the selection of approved molecular targeted therapies. However, this is often limited by its invasiveness, feasibility, and poor sample quality. Liquid biopsies provide a less invasive approach while capturing a contemporaneous and comprehensive tumor genomic profile. Recent advancements in the detection of circulating tumor DNA (ctDNA) from plasma samples at satisfactory sensitivity, specificity, and detection concordance to tumor tissues have facilitated the approval of ctDNA-based genomic profiling to be integrated into regular clinical practice. The recent approval of both single-gene and multigene assays to detect genetic biomarkers from plasma cell-free DNA (cfDNA) as companion diagnostic tools for molecular targeted therapies has transformed the therapeutic decision-making procedure for advanced solid tumors. Despite the increasing use of cfDNA-based molecular profiling, there is an ongoing debate about a ‘plasma first’ or ‘tissue first’ approach toward genomic testing for advanced solid malignancies. Both approaches present possible advantages and disadvantages, and these factors should be carefully considered to personalize and select the most appropriate genomic assay. This review focuses on the recent advancements of cfDNA-based genomic profiling assays in advanced solid tumors while highlighting the major challenges that should be tackled to formulate evidence-based guidelines in recommending the ‘right assay for the right patient at the right time’. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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23 pages, 1321 KiB  
Review
Deciphering Tumour Heterogeneity: From Tissue to Liquid Biopsy
by Pauline Gilson, Jean-Louis Merlin and Alexandre Harlé
Cancers 2022, 14(6), 1384; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061384 - 08 Mar 2022
Cited by 34 | Viewed by 5535
Abstract
Human solid malignancies harbour a heterogeneous set of cells with distinct genotypes and phenotypes. This heterogeneity is installed at multiple levels. A biological diversity is commonly observed between tumours from different patients (inter-tumour heterogeneity) and cannot be fully captured by the current consensus [...] Read more.
Human solid malignancies harbour a heterogeneous set of cells with distinct genotypes and phenotypes. This heterogeneity is installed at multiple levels. A biological diversity is commonly observed between tumours from different patients (inter-tumour heterogeneity) and cannot be fully captured by the current consensus molecular classifications for specific cancers. To extend the complexity in cancer, there are substantial differences from cell to cell within an individual tumour (intra-tumour heterogeneity, ITH) and the features of cancer cells evolve in space and time. Currently, treatment-decision making usually relies on the molecular characteristics of a limited tumour tissue sample at the time of diagnosis or disease progression but does not take into account the complexity of the bulk tumours and their constant evolution over time. In this review, we explore the extent of tumour heterogeneity with an emphasis on ITH and report the mechanisms that promote and sustain this diversity in cancers. We summarise the clinical strikes of ITH in the management of patients with cancer. Finally, we discuss the current material and technological approaches that are relevant to adequately appreciate ITH. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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14 pages, 463 KiB  
Review
Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors
by Lionel Larribère and Uwe M. Martens
Cancers 2021, 13(22), 5698; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225698 - 14 Nov 2021
Cited by 29 | Viewed by 4532
Abstract
The ability to detect minimal residual disease (MRD) after a curative-intent surgery or treatment is of paramount importance, because it offers the possibility to help guide the clinical decisions related adjuvant therapy. Thus, the earlier MRD is detected, the earlier potentially beneficial treatment [...] Read more.
The ability to detect minimal residual disease (MRD) after a curative-intent surgery or treatment is of paramount importance, because it offers the possibility to help guide the clinical decisions related adjuvant therapy. Thus, the earlier MRD is detected, the earlier potentially beneficial treatment can be proposed to patients who might need it. Liquid biopsies, and in particular the next-generation sequencing of circulating tumor DNA (ctDNA) in the blood, have been the focus of an increasing amount of research in the past years. The ctDNA detection at advanced cancer stages is practicable for several solid tumors, and complements molecular information on acquired therapy resistance. In the context of MRD, it is by definition more challenging to detect ctDNA, but it is technically achievable and provides information on treatment response and probability of relapse significantly earlier than standard imaging methods. The clinical benefit of implementing this new technique in the routine is being tested in interventional clinical trials at the moment. We propose here an update of the current use of ctDNA detection by NGS as a tool to assess the presence of MRD and improve adjuvant treatment of solid tumors. We also discuss the main limitations and medium-term perspectives of this process in the clinic. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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20 pages, 731 KiB  
Review
Liquid Biopsies beyond Mutation Calling: Genomic and Epigenomic Features of Cell-Free DNA in Cancer
by Arlou Kristina Angeles, Florian Janke, Simone Bauer, Petros Christopoulos, Anja Lisa Riediger and Holger Sültmann
Cancers 2021, 13(22), 5615; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225615 - 10 Nov 2021
Cited by 21 | Viewed by 4705
Abstract
Cell-free DNA (cfDNA) analysis using liquid biopsies is a non-invasive method to gain insights into the biology, therapy response, mechanisms of acquired resistance and therapy escape of various tumors. While it is well established that individual cancer treatment options can be adjusted by [...] Read more.
Cell-free DNA (cfDNA) analysis using liquid biopsies is a non-invasive method to gain insights into the biology, therapy response, mechanisms of acquired resistance and therapy escape of various tumors. While it is well established that individual cancer treatment options can be adjusted by panel next-generation sequencing (NGS)-based evaluation of driver mutations in cfDNA, emerging research additionally explores the value of deep characterization of tumor cfDNA genomics and fragmentomics as well as nucleosome modifications (chromatin structure), and methylation patterns (epigenomics) for comprehensive and multi-modal assessment of cfDNA. These tools have the potential to improve disease monitoring, increase the sensitivity of minimal residual disease identification, and detection of cancers at earlier stages. Recent progress in emerging technologies of cfDNA analysis is summarized, the added potential clinical value is highlighted, strengths and limitations are identified and compared with conventional targeted NGS analysis, and current challenges and future directions are discussed. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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15 pages, 829 KiB  
Review
Liquid Biopsy and Primary Brain Tumors
by Robert H. Eibl and Markus Schneemann
Cancers 2021, 13(21), 5429; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215429 - 29 Oct 2021
Cited by 27 | Viewed by 6503
Abstract
Two decades of “promising results” in liquid biopsy have led to both continuing disappointment and hope that the new era of minimally invasive, personalized analysis can be applied for better diagnosis, prognosis, monitoring, and therapy of cancer. Here, we briefly highlight the promises, [...] Read more.
Two decades of “promising results” in liquid biopsy have led to both continuing disappointment and hope that the new era of minimally invasive, personalized analysis can be applied for better diagnosis, prognosis, monitoring, and therapy of cancer. Here, we briefly highlight the promises, developments, and challenges related to liquid biopsy of brain tumors, including circulating tumor cells, cell-free nucleic acids, extracellular vesicles, and miRNA; we further discuss the urgent need to establish suitable biomarkers and the right standards to improve modern clinical management of brain tumor patients with the use of liquid biopsy. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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25 pages, 1096 KiB  
Review
Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact
by Natasha Honoré, Rachel Galot, Cédric van Marcke, Nisha Limaye and Jean-Pascal Machiels
Cancers 2021, 13(21), 5364; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215364 - 26 Oct 2021
Cited by 27 | Viewed by 5131
Abstract
One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly [...] Read more.
One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly diagnose the presence of MRD. Liquid biopsies thus have the potential to detect MRD, allowing, among other things, the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor-specific microRNA. Although liquid biopsy is increasingly studied, several technical issues still limit its clinical applicability: low sensitivity, poor standardization or reproducibility, and lack of randomized trials demonstrating its clinical benefit. Being able to detect MRD could give clinicians a more comprehensive view of the risk of relapse of their patients and could select patients requiring treatment escalation with the goal of improving cancer survival. In this review, we are discussing the different methodologies used and investigated to detect MRD in solid cancers, their respective potentials and issues, and the clinical impacts that MRD detection will have on the management of cancer patients. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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23 pages, 711 KiB  
Review
New Advances in Liquid Biopsy Technologies for Anaplastic Lymphoma Kinase (ALK)—Positive Cancer
by Matteo Villa, Geeta G. Sharma, Chiara Manfroni, Diego Cortinovis and Luca Mologni
Cancers 2021, 13(20), 5149; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205149 - 14 Oct 2021
Cited by 10 | Viewed by 2939
Abstract
Cancer cells are characterized by high genetic instability, that favors tumor relapse. The identification of the genetic causes of relapse can direct next-line therapeutic choices. As tumor tissue rebiopsy at disease progression is not always feasible, noninvasive alternative methods are being explored. Liquid [...] Read more.
Cancer cells are characterized by high genetic instability, that favors tumor relapse. The identification of the genetic causes of relapse can direct next-line therapeutic choices. As tumor tissue rebiopsy at disease progression is not always feasible, noninvasive alternative methods are being explored. Liquid biopsy is emerging as a non-invasive, easy and repeatable tool to identify specific molecular alterations and monitor disease response during treatment. The dynamic follow-up provided by this analysis can provide useful predictive information and allow prompt therapeutic actions, tailored to the genetic profile of the recurring disease, several months before radiographic relapse. Oncogenic fusion genes are particularly suited for this type of analysis. Anaplastic Lymphoma Kinase (ALK) is the dominant driver oncogene in several tumors, including Anaplastic Large-Cell Lymphoma (ALCL), Non-Small Cell Lung Cancer (NSCLC) and others. Here we review recent findings in liquid biopsy technologies, including ctDNA, CTCs, exosomes, and other markers that can be investigated from plasma samples, in ALK-positive cancers. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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26 pages, 979 KiB  
Review
Current Technologies for RNA-Directed Liquid Diagnostics
by Maria Victoria Martinez-Dominguez, Alja Zottel, Neja Šamec, Ivana Jovčevska, Can Dincer, Ulf Dietrich Kahlert and Ann-Christin Nickel
Cancers 2021, 13(20), 5060; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205060 - 10 Oct 2021
Cited by 12 | Viewed by 5654
Abstract
There is unequivocal acceptance of the variety of enormous potential liquid nucleic acid-based diagnostics seems to offer. However, the existing controversies and the increased awareness of RNA-based techniques in society during the current global COVID-19 pandemic have made the readiness of liquid nucleic [...] Read more.
There is unequivocal acceptance of the variety of enormous potential liquid nucleic acid-based diagnostics seems to offer. However, the existing controversies and the increased awareness of RNA-based techniques in society during the current global COVID-19 pandemic have made the readiness of liquid nucleic acid-based diagnostics for routine use a matter of concern. In this regard—and in the context of oncology—our review presented and discussed the status quo of RNA-based liquid diagnostics. We summarized the technical background of the available assays and benchmarked their applicability against each other. Herein, we compared the technology readiness level in the clinical context, economic aspects, implementation as part of routine point-of-care testing as well as performance power. Since the preventive care market is the most promising application sector, we also investigated whether the developments predominantly occur in the context of early disease detection or surveillance of therapy success. In addition, we provided a careful view on the current biotechnology investment activities in this sector to indicate the most attractive strategies for future economic success. Taken together, our review shall serve as a current reference, at the interplay of technology, clinical use and economic potential, to guide the interested readers in this rapid developing sector of precision medicine. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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16 pages, 1097 KiB  
Review
Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma
by Sutpirat Moonmuang, Parunya Chaiyawat, Salinee Jantrapirom, Dumnoensun Pruksakorn and Luca Lo Piccolo
Cancers 2021, 13(16), 4214; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164214 - 21 Aug 2021
Cited by 11 | Viewed by 2903
Abstract
Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. [...] Read more.
Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers. However, the potential of circulating long ncRNAs (c-lncRNAs) to be markers in osteosarcoma (OS) is still elusive. In this study we performed a systematic review to identify thirteen c-lncRNAs whose altered expression in blood associate with OS. We herein discuss the potential impact that these c-lncRNAs may have on clinical decision-making in the management of OS. Overall, we aimed to provide novel insights that can contribute to the development of future precision medicine in oncology. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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26 pages, 678 KiB  
Review
Urinary Extracellular Vesicles as Potential Biomarkers for Urologic Cancers: An Overview of Current Methods and Advances
by Catarina Lourenço, Vera Constâncio, Rui Henrique, Ângela Carvalho and Carmen Jerónimo
Cancers 2021, 13(7), 1529; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13071529 - 26 Mar 2021
Cited by 20 | Viewed by 2687
Abstract
Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have [...] Read more.
Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of biomarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease management. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies. Full article
(This article belongs to the Special Issue Liquid Nucleic Acid-Based Biomarkers in Solid Tumors)
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