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Brain : a Journal of Neurology May 2023This article reviews recent developments in the application of cell-free DNA-based liquid biopsies to neurological diseases. Over the past few decades, an explosion of... (Review)
Review
This article reviews recent developments in the application of cell-free DNA-based liquid biopsies to neurological diseases. Over the past few decades, an explosion of interest in the use of accessible biofluids to identify and track molecular disease has revolutionized the fields of oncology, prenatal medicine and others. More recently, technological advances in signal detection have allowed for informative analysis of biofluids that are typically sparse in cells and other circulating components, such as CSF. In parallel, advancements in epigenetic profiling have allowed for novel applications of liquid biopsies to diseases without characteristic mutational profiles, including many degenerative, autoimmune, inflammatory, ischaemic and infectious disorders. These events have paved the way for a wide array of neurological conditions to benefit from enhanced diagnostic, prognostic, and treatment abilities through the use of liquid biomarkers: a 'liquid biopsy' approach. This review includes an overview of types of liquid biopsy targets with a focus on circulating cell-free DNA, methods used to identify and probe potential liquid biomarkers, and recent applications of such biomarkers to a variety of complex neurological conditions including CNS tumours, stroke, traumatic brain injury, Alzheimer's disease, epilepsy, multiple sclerosis and neuroinfectious disease. Finally, the challenges of translating liquid biopsies to use in clinical neurology settings-and the opportunities for improvement in disease management that such translation may provide-are discussed.
Topics: Pregnancy; Female; Humans; Cell-Free Nucleic Acids; Biomarkers, Tumor; Liquid Biopsy; Mutation; Neurology
PubMed: 36408894
DOI: 10.1093/brain/awac438 -
Cell Reports. Medicine Oct 2023The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive... (Review)
Review
The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.
Topics: Humans; Liquid Biopsy; Cell-Free Nucleic Acids; Biomarkers; Neoplastic Cells, Circulating; Extracellular Vesicles
PubMed: 37716353
DOI: 10.1016/j.xcrm.2023.101198 -
Molecular Cancer May 2022Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. One of the main challenges in the management of OC is the late clinical presentation of disease... (Review)
Review
Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. One of the main challenges in the management of OC is the late clinical presentation of disease that results in poor survival. Conventional tissue biopsy methods and serological biomarkers such as CA-125 have limited clinical applications. Liquid biopsy is a novel sampling method that analyzes distinctive tumour components released into the peripheral circulation, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free RNA (cfRNA), tumour-educated platelets (TEPs) and exosomes. Increasing evidence suggests that liquid biopsy could enhance the clinical management of OC by improving early diagnosis, predicting prognosis, detecting recurrence, and monitoring response to treatment. Capturing the unique tumour genetic landscape can also guide treatment decisions and the selection of appropriate targeted therapies. Key advantages of liquid biopsy include its non-invasive nature and feasibility, which allow for serial sampling and longitudinal monitoring of dynamic tumour changes over time. In this review, we outline the evidence for the clinical utility of each liquid biopsy component and review the advantages and current limitations of applying liquid biopsy in managing ovarian cancer. We also highlight future directions considering the current challenges and explore areas where more studies are warranted to elucidate its emerging clinical potential.
Topics: Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Circulating Tumor DNA; Female; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Ovarian Neoplasms
PubMed: 35545786
DOI: 10.1186/s12943-022-01588-8 -
Nature Reviews. Cancer Feb 2023In recent years, exceptional technological advances have enabled the identification and interrogation of rare circulating tumour cells (CTCs) from blood samples of... (Review)
Review
In recent years, exceptional technological advances have enabled the identification and interrogation of rare circulating tumour cells (CTCs) from blood samples of patients, leading to new fields of research and fostering the promise for paradigm-changing, liquid biopsy-based clinical applications. Analysis of CTCs has revealed distinct biological phenotypes, including the presence of CTC clusters and the interaction between CTCs and immune or stromal cells, impacting metastasis formation and providing new insights into cancer vulnerabilities. Here we review the progress made in understanding biological features of CTCs and provide insight into exploiting these developments to design future clinical tools for improving the diagnosis and treatment of cancer.
Topics: Humans; Neoplastic Cells, Circulating; Liquid Biopsy; Biology
PubMed: 36494603
DOI: 10.1038/s41568-022-00536-4 -
Journal of Translational Medicine Feb 2023Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and... (Review)
Review
Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics.
Topics: Humans; Early Detection of Cancer; Quality of Life; Neoplasms; Liquid Biopsy; Forecasting
PubMed: 36774504
DOI: 10.1186/s12967-023-03960-8 -
Molecular Cancer Feb 2023Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages,... (Review)
Review
Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.
Topics: Humans; Carcinoma, Renal Cell; Liquid Biopsy; Cell-Free Nucleic Acids; Kidney Neoplasms; Biomarkers, Tumor; Neoplastic Cells, Circulating
PubMed: 36810071
DOI: 10.1186/s12943-023-01745-7 -
Clinical Epigenetics Sep 2022Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is... (Review)
Review
Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA Methylation; Humans; Liquid Biopsy; Lung Neoplasms; Prognosis
PubMed: 36153611
DOI: 10.1186/s13148-022-01337-0 -
Nature Medicine Nov 2023Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the...
Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. Our assay provided a robust proxy for transcriptional activity, allowing us to infer the expression levels of diagnostic markers and drug targets, measure the activity of therapeutically targetable transcription factors and detect epigenetic mechanisms of resistance. This proof-of-concept study in advanced cancers shows how plasma epigenomic profiling has the potential to unlock clinically actionable information that is currently accessible only via direct tissue sampling.
Topics: Humans; Epigenomics; Biomarkers, Tumor; Neoplasms; Circulating Tumor DNA; Liquid Biopsy; Mutation
PubMed: 37865722
DOI: 10.1038/s41591-023-02605-z -
Genome Medicine Mar 2020The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with... (Review)
Review
The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cell-resolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine.
Topics: Animals; Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating
PubMed: 32192534
DOI: 10.1186/s13073-020-00728-3 -
Clinical Chemistry Dec 2022The current methodology used to detect, diagnose, and monitor many types of cancers requires invasive tissue biopsy testing. Recently, liquid biopsy using blood, plasma,... (Review)
Review
BACKGROUND
The current methodology used to detect, diagnose, and monitor many types of cancers requires invasive tissue biopsy testing. Recently, liquid biopsy using blood, plasma, urine, saliva, and various other bodily fluids has shown utility to solve many issues associated with tissue biopsy. Blood/plasma has received most of the attention within the liquid biopsy field, however, obtaining blood samples from patients is still somewhat invasive and requires trained professionals. Using urine to detect cell-free DNA cancer biomarkers offers a truly non-invasive sampling method that can be easily and reproducibly conducted by patients.
CONTENT
Novel technologies and approaches have made the detection of small quantities of cell-free tumor DNA of varying lengths possible. Recent studies using urine circulating tumor DNA to detect cancer mutations and other biomarkers have shown sensitivity comparable to blood/plasma cell-free DNA liquid biopsy for many cancer types. Thus, urine cell-free DNA liquid biopsy may replace or provide supplementary information to tissue/blood biopsies. Further investigation with larger patient cohorts and standardization of pre-analytical factors is necessary to determine the utility of urine cell-free DNA liquid biopsy for cancer detection, diagnosis, and monitoring in a clinical setting.
SUMMARY
In this mini-review we discuss the biological aspects of cell-free DNA in urine, numerous studies using urine cell-free DNA to detect urological cancers, and recent studies using urine cell-free DNA to detect and monitor non-urological cancers including lung, breast, colorectal, and other cancers.
Topics: Humans; Cell-Free Nucleic Acids; Liquid Biopsy; Circulating Tumor DNA; Biomarkers, Tumor; Urologic Neoplasms
PubMed: 36213956
DOI: 10.1093/clinchem/hvac122