Liquid Biopsy beyond Circulating Tumor Cells and Cell-Free DNA

2019 ◽  
Vol 63 (6) ◽  
pp. 479-488 ◽  
Author(s):  
Susana Junqueira-Neto ◽  
Inês A. Batista ◽  
José Luís Costa ◽  
Sónia A. Melo
Keyword(s):  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Great Promise ◽  
Genetic Profile ◽  
Clonal Heterogeneity ◽  
Surgical Biopsy ◽  
Non Invasive ◽  
Metastatic Lesions ◽  
Detection Tool

Liquid biopsy represents the analysis of tumor-derived material in the blood and other body fluids of cancer patients. This portrays a minimally invasive detection tool for molecular biomarkers. Liquid biopsy has emerged as a complementary or alternative method to surgical biopsy. This non-invasive detection tool overcomes the recurrent problems in the clinical assessment of tumors that stem from the lack of accessibility to the tumor tissue and its clonal heterogeneity. Moreover, body fluid-derived components have shown to reflect the genetic profile of both primary and metastatic lesions and provide a real-time monitoring of tumor dynamics, representing a great promise for personalized medicine. This review will highlight the latest breakthroughs and the current applications of several tumor-derived biomarkers that can be found in body fluids. The authors will focus on tumor-derived exosomes, tumor-educated platelets, and circulating tumor miRNAs and mRNAs, and how these can be used for tumor detection.

scholarly journals The Translational Status of Cancer Liquid Biopsies

2019 ◽  
Author(s):  
Sinisa Bratulic ◽  
Francesco Gatto ◽  
Jens Nielsen
Keyword(s):  
Treatment Outcomes ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Biomarker Research ◽  
Successes And Challenges

Abstract Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research.

scholarly journals Liquid biopsy for patients with IBD-associated neoplasia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hideaki Kinugasa ◽  
Sakiko Hiraoka ◽  
Kazuhiro Nouso ◽  
Shumpei Yamamoto ◽  
Mami Hirai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Target Genes ◽  
Tumor Tissue ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Inflammatory Bowel

Abstract Background It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

scholarly journals Liquid Biopsy Biomarkers in Bladder Cancer: A Current Need for Patient Diagnosis and Monitoring

2018 ◽  
Vol 19 (9) ◽  
pp. 2514 ◽  
Author(s):  
Iris Lodewijk ◽  
Marta Dueñas ◽  
Carolina Rubio ◽  
Ester Munera-Maravilla ◽  
Cristina Segovia ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Liquid Biopsy ◽  
Disease Surveillance ◽  
Great Promise ◽  
Liquid Biopsies ◽  
Recurrence Rates ◽  
Invasive Approach ◽  
Non Invasive ◽  
Social Challenge ◽  
High Incidence

Bladder Cancer (BC) represents a clinical and social challenge due to its high incidence and recurrence rates, as well as the limited advances in effective disease management. Currently, a combination of cytology and cystoscopy is the routinely used methodology for diagnosis, prognosis and disease surveillance. However, both the poor sensitivity of cytology tests as well as the high invasiveness and big variation in tumour stage and grade interpretation using cystoscopy, emphasizes the urgent need for improvements in BC clinical guidance. Liquid biopsy represents a new non-invasive approach that has been extensively studied over the last decade and holds great promise. Even though its clinical use is still compromised, multiple studies have recently focused on the potential application of biomarkers in liquid biopsies for BC, including circulating tumour cells and DNA, RNAs, proteins and peptides, metabolites and extracellular vesicles. In this review, we summarize the present knowledge on the different types of biomarkers, their potential use in liquid biopsy and clinical applications in BC.

scholarly journals New Advances in Liquid Biopsy Technologies for Anaplastic Lymphoma Kinase (ALK)—Positive Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5149
Author(s):  
Matteo Villa ◽  
Geeta G. Sharma ◽  
Chiara Manfroni ◽  
Diego Cortinovis ◽  
Luca Mologni
Keyword(s):  
Anaplastic Lymphoma Kinase ◽  
Liquid Biopsy ◽  
Large Cell ◽  
Alternative Methods ◽  
Genetic Profile ◽  
Disease Response ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Non Invasive ◽  
Alk Positive

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.

scholarly journals Blood-Based Liquid Biopsy for Comprehensive Cancer Genomic Profiling Using Next-Generation Sequencing: An Emerging Paradigm for Non-invasive Cancer Detection and Management in Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Kristina M. Kruglyak ◽  
Jason Chibuk ◽  
Lisa McLennan ◽  
Prachi Nakashe ◽  
Gilberto E. Hernandez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Genomic Profiling ◽  
Next Generation ◽  
Blood Draw ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Non Invasive ◽  
Generation Sequencing

This proof-of-concept study demonstrates that blood-based liquid biopsy using next generation sequencing of cell-free DNA can non-invasively detect multiple classes of genomic alterations in dogs with cancer, including alterations that originate from spatially separated tumor sites. Eleven dogs with a variety of confirmed cancer diagnoses (including localized and disseminated disease) who were scheduled for surgical resection, and five presumably cancer-free dogs, were enrolled. Blood was collected from each subject, and multiple spatially separated tumor tissue samples were collected during surgery from 9 of the cancer subjects. All samples were analyzed using an advanced prototype of a novel liquid biopsy test designed to non-invasively interrogate multiple classes of genomic alterations for the detection, characterization, and management of cancer in dogs. In five of the nine cancer patients with matched tumor and plasma samples, pre-surgical liquid biopsy testing identified genomic alterations, including single nucleotide variants and copy number variants, that matched alterations independently detected in corresponding tumor tissue samples. Importantly, the pre-surgical liquid biopsy test detected alterations observed in spatially separated tissue samples from the same subject, demonstrating the potential of blood-based testing for comprehensive genomic profiling of heterogeneous tumors. Among the three patients with post-surgical blood samples, genomic alterations remained detectable in one patient with incomplete tumor resection, suggesting utility for non-invasive detection of minimal residual disease following curative-intent treatment. Liquid biopsy allows for non-invasive profiling of cancer-associated genomic alterations with a simple blood draw and has potential to overcome the limitations of tissue-based testing posed by tissue-level genomic heterogeneity.

scholarly journals The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yunjing Zhang ◽  
Ying Wang ◽  
Xinwan Su ◽  
Ping Wang ◽  
Weiqiang Lin
Keyword(s):  
Liquid Biopsy ◽  
Screening Tool ◽  
Clinical Medicine ◽  
High Specificity ◽  
Circular Rna ◽  
Body Fluids ◽  
Precision Oncology ◽  
Clinical Practices ◽  
Non Invasive ◽  
Human Cancers

Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of current invasive tissue examinations in precision oncology. Circular RNA (circRNA) is a recent, novel, and attractive liquid biomarker showing stability, abundance, and high specificity in various diseases, especially in human cancers. This review focused on the emerging potential of human circRNA in body fluids as the liquid biopsy biomarkers for cancers and the methods used to detect the circRNA expression and summarized the construction of circRNA biomarkers in body fluids for treating human cancers and their limitations before they become part of routine clinical medicine. Furthermore, the future opportunities and challenges of translating circRNAs in liquid biopsy into clinical practices were explored.

scholarly journals Updates on liquid biopsy: current trends and future perspectives for clinical application in solid tumors

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pamela Pinzani ◽  
Valeria D’Argenio ◽  
Marzia Del Re ◽  
Cristina Pellegrini ◽  
Federico Cucchiara ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Molecular Profile ◽  
Disease Evolution ◽  
Non Invasive ◽  
Metastatic Lesions ◽  
Current Trends ◽  
Available Information ◽  
Cancer Côlon ◽  
Tumor Dna

Abstract Despite advances in screening and therapeutics cancer continues to be one of the major causes of morbidity and mortality worldwide. The molecular profile of tumor is routinely assessed by surgical or bioptic samples, however, genotyping of tissue has inherent limitations: it represents a single snapshot in time and it is subjected to spatial selection bias owing to tumor heterogeneity. Liquid biopsy has emerged as a novel, non-invasive opportunity of detecting and monitoring cancer in several body fluids instead of tumor tissue. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), RNA (mRNA and microRNA), microvesicles, including exosomes and tumor “educated platelets” were recently identified as a source of genomic information in cancer patients which could reflect all subclones present in primary and metastatic lesions allowing sequential monitoring of disease evolution. In this review, we summarize the currently available information concerning liquid biopsy in breast cancer, colon cancer, lung cancer and melanoma. These promising issues still need to be standardized and harmonized across laboratories, before fully adopting liquid biopsy approaches into clinical practice.

scholarly journals P1.29: “Real World” Use of Liquid Biopsy in Patients With Lung Adenocarcinoma and Correlation With Tumor Tissue Genetic Profile

2016 ◽  
Vol 11 (10) ◽  
pp. S199-S200
Author(s):  
Edgardo S. Santos ◽  
Luis E. Raez ◽  
Lilibeth Castillero ◽  
Camila Marana ◽  
Brian Hunis
Keyword(s):  
Lung Adenocarcinoma ◽  
Real World ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Genetic Profile

Cell free DNA as an evolving liquid biopsy biomarker for initial diagnosis and therapeutic nursing in Cancer- An evolving aspect in Medical Biotechnology

2020 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Nuclear Dna ◽  
Fragment Size ◽  
Body Fluids ◽  
Response To Therapy ◽  
Significant Information ◽  
Cell Free Dna ◽  
Free Dna

: Cell-free DNA (cfDNA) is present in numerous body fluids in addition to initiates generally from blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the nonsolid biological tissue by revealing of circulating cells, cell free DNA etc. that enter body fluids. Since, cancer cells disengage from compact tumors circulate in peripheral blood, evaluating blood of cancer patients holds the opportunities for capture and molecular level analysis of various tumor-derived constituents. Cell free DNA samples can deliver a significant perceptions into oncology, for instance tumor heterogeneity, instantaneous tumor development, response to therapy and treatment, comprising immunotherapy and mechanisms of cancer metastasis. Malignant growth at any phase can outhouse tumor cells in addition to fragments of neoplasticity causing DNA into circulatory system giving noble sign of mutation in the tumor at sampling time. Liquid biopsy distinguishes diverse blood based evolving biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA) and exosomes. Cell free DNA are little DNA fragments found circulating in plasma or serum, just as other fluids present in our body. Cell free DNA involves primarily double stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the lumen of vesicles. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or release of DNA from the tumor cells into circulation. The evolution of innovations, refinement and improvement in therapeutics for determination of cfDNA fragment size and its distribution provide significant information related with pathological conditions of the cell, thus emerging as promising indicator for clinical output in medical biotechnology.

Optimization of Extraction Parameters of Reverse Iontophoretic Determination of Blood Glucose in an Artificial Skin Model

2020 ◽  
Vol 16 (6) ◽  
pp. 722-737
Author(s):  
Cigdem Yengin ◽  
Emrah Kilinc ◽  
Fatma Gulay Der ◽  
Mehmet Can Sezgin ◽  
Ilayda Alcin
Keyword(s):  
Ionic Strength ◽  
Body Fluids ◽  
Extraction Time ◽  
Artificial Skin ◽  
Dialysis Membrane ◽  
Skin Model ◽  
Non Invasive ◽  
Electrode Distance ◽  
Experimental Parameters

Background: Reverse İontophoresis (RI) is one of the promising non-invasive technologies. It relies on the transition of low magnitude current through the skin and thus glucose measurement becomes possible as it is extracted from the surface during this porter current flow. Objective: This paper deals with the development and optimization of an RI determination method for glucose. CE dialysis membrane based artificial skin model was developed and the dependence of RI extraction on various experimental parameters was investigated. Method: Dependence of RI extraction performance on noble electrodes (platinum, silver, palladium, ruthenium, rhodium) was checked with CA, CV and DPV, in a wide pH and ionic strength range. Optimizations on inter-electrode distance, potential type and magnitude, extraction time, gel type, membrane MWCO, usage frequency, pretreatment, artificial body fluids were performed. Results: According to the optimized results, the inter-electrode distance was 7.0 mm and silver was the optimum noble metal. Optimum pH and ionic strength were achieved with 0.05M PBS at pH 7.4. Higher glucose yields were obtained with DPV, while CA and CV achieved almost the same levels. During CA, +0.5V achieved the highest glucose yield and higher potential even caused a decrease. Glucose levels could be monitored for 24 hours. CMC gel was the optimum collection media. Pretreated CE membrane with 12kD MWCO was the artificial skin model. Pretreatment affected the yields while its condition caused no significant difference. Except PBS solution (simulated as artificial plasma), among the various artificial simulated body fluids, intestinal juice formulation (AI) and urine formulation U2 were the optimum extraction media, respectively. Conclusion: In this study, various experimental parameters (pretereatment procedure, type and MWCO values of membranes, inter-electrode distance, electrode material, extraction medium solvents, ionic strength and pH, collection medium gel type, extraction potential type and magnitude, extraction time and etc) were optimized for the non-invasive RI determination of glucose in a CE dialysis membrane-based artificial skin model and various simulated artificial body fluids.

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