scholarly journals Liquid Biopsy in Gastrointestinal Cancers

Diagnostics ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 75 ◽  
Author(s):  
Aman Saini ◽  
Yash Pershad ◽  
Hassan Albadawi ◽  
Malia Kuo ◽  
Sadeer Alzubaidi ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Disease Surveillance ◽  
Biological Fluid ◽  
Genetic Material ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Gastrointestinal Cancers ◽  
New Paradigm ◽  
Liquid Biopsies ◽  
Biopsy Material

Liquid biopsy is the sampling of any biological fluid in an effort to enrich and analyze a tumor’s genetic material. Peripheral blood remains the most studied liquid biopsy material, with circulating tumor cells (CTC’s) and circulating tumor DNA (ctDNA) allowing the examination and longitudinal monitoring of a tumors genetic landscape. With applications in cancer screening, prognostic stratification, therapy selection and disease surveillance, liquid biopsy represents an exciting new paradigm in the field of cancer diagnostics and offers a less invasive and more comprehensive alternative to conventional tissue biopsy. Here, we examine liquid biopsies in gastrointestinal cancers, specifically colorectal, gastric, and pancreatic cancers, with an emphasis on applications in diagnostics, prognostics and therapeutics.

scholarly journals Liquid Biopsies in Solid Cancers: Implementation in a Nordic Healthcare System

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1861
Author(s):  
Oddmund Nordgård ◽  
Rakel Brendsdal Forthun ◽  
Morten Lapin ◽  
Bjørn Henning Grønberg ◽  
Karl Henning Kalland ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Cancer Biology ◽  
Growth Factor Receptor ◽  
Relevant Information ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Current Evidence ◽  
Liquid Biopsies ◽  
Clinical Role

Liquid biopsies have emerged as a potential new diagnostic tool, providing detailed information relevant for characterization and treatment of solid cancers. We here present an overview of current evidence supporting the clinical relevance of liquid biopsy assessments. We also discuss the implementation of liquid biopsies in clinical studies and their current and future clinical role, with a special reference to the Nordic healthcare systems. Our considerations are restricted to the most established liquid biopsy specimens: circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Both ctDNA and CTCs have been used for prognostic stratification, treatment choices, and treatment monitoring in solid cancers. Several recent publications also support the role of ctDNA in early cancer detection. ctDNA seems to provide more robust clinically relevant information in general, whereas CTCs have the potential to answer more basic questions related to cancer biology and metastasis. Epidermal growth factor receptor-directed treatment of non-small-cell lung cancer represents a clinical setting where ctDNA already has entered the clinic. The role of liquid biopsies in treatment decisions, standardization of methods, diagnostic performance and the need for further research, as well as cost and regulatory issues were identified as factors that influence further integration in the clinic. In conclusion, substantial evidence supports the clinical utility of liquid biopsies in cancer diagnostics, but further research is still required for a more general application in clinical practice.

scholarly journals Evolving Clinical Utility of Liquid Biopsy in Gastrointestinal Cancers

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1164 ◽  
Author(s):  
Jacobson ◽  
Munding ◽  
Hayden ◽  
Levy ◽  
Kuzel ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Clinical Evidence ◽  
Circulating Tumor Dna ◽  
Gastrointestinal Cancers ◽  
Liquid Biopsies ◽  
Colon And Rectum ◽  
Increased Sensitivity ◽  
Tumor Dna ◽  
Genomic Material

Room for improvement exists regarding recommendations for screening, staging, therapy selection, and frequency of surveillance of gastrointestinal cancers. Screening is costly and invasive, improved staging demands increased sensitivity and specificity to better guide therapy selection. Surveillance requires increased sensitivity for earlier detection and precise management of recurrences. Peripherally collected blood-based liquid biopsies enrich and analyze circulating tumor cells and/or somatic genomic material, including circulating tumor DNA along with various subclasses of RNA. Such assays have the potential to impact clinical practice at multiple stages of management in gastrointestinal cancers. This review summarizes current basic and clinical evidence for the utilization of liquid biopsy in cancers of the esophagus, pancreas, stomach, colon, and rectum. Technical aspects of various liquid biopsy methodologies and targets are reviewed and evidence supporting current commercially available assays is examined. Finally, current clinical applicability, potential future uses, and pitfalls of applying liquid biopsy to the screening, staging and therapeutic management of these diseases are discussed.

scholarly journals Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2101
Author(s):  
Ângela Carvalho ◽  
Gabriela Ferreira ◽  
Duarte Seixas ◽  
Catarina Guimarães-Teixeira ◽  
Rui Henrique ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Lab On A Chip ◽  
Microfluidic Devices ◽  
Early Recurrence ◽  
Circulating Tumor Dna ◽  
Clinical Validation ◽  
Liquid Biopsies ◽  
Lung Cancer Patients

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.

scholarly journals Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA

2021 ◽  
Vol 12 ◽  
Author(s):  
Megan E. Barefoot ◽  
Netanel Loyfer ◽  
Amber J. Kiliti ◽  
A. Patrick McDeed ◽  
Tommy Kaplan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Types ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Tissue Homeostasis ◽  
Specific Cell ◽  
Cell Type ◽  
Liquid Biopsies ◽  
Methylated Dna ◽  
Cell Type Specific

Detection of cellular changes in tissue biopsies has been the basis for cancer diagnostics. However, tissue biopsies are invasive and limited by inaccuracies due to sampling locations, restricted sampling frequency, and poor representation of tissue heterogeneity. Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA (cfDNA) fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses. In addition to host-derived cfDNA, changes in cancer cells can be detected from cell-free, circulating tumor DNA (ctDNA) by monitoring DNA mutations carried by cancer cells. Here, we will discuss computational approaches to identify and validate robust biomarkers of changed tissue homeostasis using cell-free, methylated DNA in the circulation. We highlight studies performing genome-wide profiling of cfDNA methylation and those that combine genetic and epigenetic markers to further identify cell-type specific signatures. Finally, we discuss opportunities and current limitations of these approaches for implementation in clinical oncology.

scholarly journals Liquid Biopsy in Melanoma: Significance in Diagnostics, Prediction and Treatment Monitoring

2021 ◽  
Vol 22 (18) ◽  
pp. 9714
Author(s):  
Paula Kamińska ◽  
Karolina Buszka ◽  
Maciej Zabel ◽  
Michał Nowicki ◽  
Catherine Alix-Panabières ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Treatment Monitoring ◽  
Cancer Diagnostics ◽  
Continuous Control ◽  
Patient Stratification ◽  
Sample Collection ◽  
Common Term ◽  
Tumor Dna ◽  
Selection Of

Liquid biopsy is a common term referring to circulating tumor cells and other biomarkers, such as circulating tumor DNA (ctDNA) or extracellular vesicles. Liquid biopsy presents a range of clinical advantages, such as the low invasiveness of the blood sample collection and continuous control of the tumor progression. In addition, this approach enables the mechanisms of drug resistance to be determined in various methods of cancer treatment, including immunotherapy. However, in the case of melanoma, the application of liquid biopsy in patient stratification and therapy needs further investigation. This review attempts to collect all of the relevant and recent information about circulating melanoma cells (CMCs) related to the context of malignant melanoma and immunotherapy. Furthermore, the biology of liquid biopsy analytes, including CMCs, ctDNA, mRNA and exosomes, as well as techniques for their detection and isolation, are also described. The available data support the notion that thoughtful selection of biomarkers and technologies for their detection can contribute to the development of precision medicine by increasing the efficacy of cancer diagnostics and treatment.

scholarly journals ctDNAtools: An R package to work with sequencing data of circulating tumor DNA

2020 ◽  
Author(s):  
Amjad Alkodsi ◽  
Leo Meriranta ◽  
Annika Pasanen ◽  
Sirpa Leppä
Keyword(s):  
Residual Disease ◽  
Fragment Size ◽  
R Package ◽  
Monte Carlo Sampling ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Sequencing Data ◽  
Liquid Biopsies ◽  
Tumor Dna

AbstractSummarySequencing of cell-free DNA (cfDNA) including circulating tumor DNA (ctDNA) in minimally-invasive liquid biopsies is rapidly maturing towards clinical utility for cancer diagnostics. However, the publicly available bioinformatics tools for the specialized analysis of ctDNA sequencing data are still scarce. Here, we present the ctDNAtools R package, which provides functionalities for testing minimal residual disease (MRD) and analyzing cfDNA fragmentation. MRD detection in ctDNAtools utilizes a Monte Carlo sampling approach to test ctDNA positivity through tracking a set of pre-detected reporter mutations in follow-up samples. Additionally, ctDNAtools includes various functionalities to study cfDNA fragment size histograms, profiles and fragment ends patterns.AvailabilityThe ctDNAtools package is freely available under MIT license at https://github.com/alkodsi/ctDNAtools.

scholarly journals TECHNICAL ASPECTS OF LIQUID BIOPSY: INFLUENCE OF PREANALYTICAL PARAMETERS ON THE CONCENTRATION OF CIRCULATING TUMOR DNA IN PLASMA OF CANCER PATIENTS

2020 ◽  
Vol 66 (4) ◽  
pp. 391-397
Author(s):  
T. Sokolova ◽  
T. Laidus ◽  
R. Meerovich ◽  
K. Zagorodnev ◽  
Aleksandr Martyanov ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Distant Metastases ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Braf V600e ◽  
Nucleotide Substitutions ◽  
Non Invasive ◽  
Intrapatient Variability ◽  
Lung Adenocarcinomas ◽  
Tumor Dna

«Liquid biopsy» is gradually becoming a mandatory procedure in cancer diagnostics. The aim of this procedure is to detect and monitor tumor-specific markers in various body fluids (blood, urine, pleural fluid, etc.). Significant efforts have been made to convert the most common mutational tests (EGFR, KRAS, BRAF) into non-invasive procedures. Despite some advantages, “liquid biopsy” is still not equivalent to traditional tissue analysis due to limited sensitivity and specificity; it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. We intend to improve the performance of liquid biopsy for detection of a number of clinically relevant mutations (EGFR: ex19del and L858R; KRAS: 12, 13, 61, 146 codon nucleotide substitutions; BRAF: V600E). 417 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in the circulating tumor DNA (ctDNA). Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (24%) melanoma cases. The proportion of mutation-positive plasma cases was tended to be higher in the group of patients with distant metastases compared to subjects with localized disease [34/56 (61%) vs. 5/15 (33%), р = 0.058]. 86 patients provided their blood at 9.00 (morning) and at 16.00 (afternoon). In addition, blood-takes were performed before and 15 minutes after usual breakfast as well as before and 15 minutes after moderate physical exercise. The detection rate of cancer-specific mutations in plasma was not significantly correlated with described above circumstances of blood-take. Meanwhile, the noticeable intrapatient variability of circulating mutation success rate has been detected. Thus, depending on clinical circumstances, at least negative ctDNA tests could be advised to be repeated in some patients, in order to ensure the reliability of results.

scholarly journals Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5825
Author(s):  
Kate I. Glennon ◽  
Mahafarin Maralani ◽  
Narges Abdian ◽  
Antoine Paccard ◽  
Laura Montermini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Liquid Biopsy ◽  
Renal Cell ◽  
Somatic Mutations ◽  
Circulating Tumor Dna ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Disease Evolution ◽  
Ctdna Analysis

Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.

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 Liquid biopsy: one cell at a time

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Su Bin Lim ◽  
Wen Di Lee ◽  
Jyothsna Vasudevan ◽  
Wan-Teck Lim ◽  
Chwee Teck Lim
Keyword(s):  
Single Cell ◽  
Liquid Biopsy ◽  
Temporal Dynamics ◽  
Genetic Material ◽  
Cellular Heterogeneity ◽  
Sources Of Information ◽  
Liquid Biopsies ◽  
Technological Developments ◽  
Clinically Significant ◽  
Tissue Specimens

Abstract As an alternative target to surgically resected tissue specimens, liquid biopsy has gained much attention over the past decade. Of the various circulating biomarkers, circulating tumor cells (CTCs) have particularly opened new windows into the metastatic cascade, with their functional, biochemical, and biophysical properties. Given the extreme rarity of intact CTCs and the associated technical challenges, however, analyses have been limited to bulk-cell strategies, missing out on clinically significant sources of information from cellular heterogeneity. With recent technological developments, it is now possible to probe genetic material of CTCs at the single-cell resolution to study spatial and temporal dynamics in circulation. Here, we discuss recent transcriptomic profiling efforts that enabled single-cell characterization of patient-derived CTCs spanning diverse cancer types. We further highlight how expression data of these putative biomarkers have advanced our understanding of metastatic spectrum and provided a basis for the development of CTC-based liquid biopsies to track, monitor, and predict the efficacy of therapy and any emergent resistance.

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