scholarly journals ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1989
Author(s):  
Laura Escudero ◽  
Francisco Martínez-Ricarte ◽  
Joan Seoane
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Cancer ◽  
Liquid Biopsy ◽  
Therapeutic Strategy ◽  
Residual Disease ◽  
Imaging Techniques ◽  
Prognostic Information ◽  
Tumour Heterogeneity ◽  
Diagnosis And Prognosis ◽  
Cns Malignancies

The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice.

scholarly journals Recent Advances in Liquid Biopsy of Brain Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunyun An ◽  
Fei Fan ◽  
Xiaobing Jiang ◽  
Kun Sun
Keyword(s):  
Cerebrospinal Fluid ◽  
Early Diagnosis ◽  
Cancer Patients ◽  
Brain Cancer ◽  
Liquid Biopsy ◽  
Causes Of Death ◽  
Survival Rates ◽  
Relapse Prediction ◽  
Clinical Benefits ◽  
The Brain

Brain cancers are among the top causes of death worldwide. Although, the survival rates vary widely depending on the type of the tumor, early diagnosis could generally benefit in better prognosis outcomes of the brain cancer patients. Conventionally, neuroimaging and biopsy are the most widely used approaches in diagnosis, subtyping, and prognosis monitoring of brain cancers, while emerging liquid biopsy assays using peripheral blood or cerebrospinal fluid have demonstrated many favorable characteristics in this task, especially due to their minimally invasive and easiness in sampling nature. Here, we review the recent studies in the liquid biopsy of brain cancers. We discuss the methodologies and performances of various assays on diagnosis, tumor subtyping, relapse prediction as well as prognosis monitoring in brain cancers, which approaches have made a big step toward clinical benefits of brain cancer patients.

scholarly journals Liquid Biopsy: The Unique Test for Chasing the Genetics of Solid Tumors

2020 ◽  
Vol 13 ◽  
pp. 251686572090405 ◽  
Author(s):  
Seyed Mohammad Kazem Aghamir ◽  
Ramin Heshmat ◽  
Mehdi Ebrahimi ◽  
Fatemeh Khatami
Keyword(s):  
Cerebrospinal Fluid ◽  
Nucleic Acids ◽  
Tumor Cells ◽  
Cancer Diagnosis ◽  
Liquid Biopsy ◽  
Blood Test ◽  
Genetic Alterations ◽  
Circular Dna ◽  
Diagnosis And Prognosis ◽  
Game Changer

Blood test is a kind of liquid biopsy that checks cancer cells or cancer nucleic acids circulating freely from cells in the blood. A liquid biopsy may be used to distinguish cancer at early stages and it could be a game-changer for both cancer diagnosis and prognosis strategies. Liquid biopsy tests consider several tumor components, such as DNA, RNA, proteins, and the tiny vesicles originating from tumor cells. Actually, liquid biopsy signifies the genetic alterations of tumors through nucleic acids or cells in various body fluids, including blood, urine, cerebrospinal fluid, or saliva in a noninvasive manner. In this review, we present an overall description of liquid biopsy in which circulating tumor cells, cell-free nucleic acids, exosomes, and extrachromosomal circular DNA are included.

Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma

Blood ◽  
2021 ◽  
Author(s):  
Leo Meriranta ◽  
Amjad Alkodsi ◽  
Annika Pasanen ◽  
Maija Lepistö ◽  
Parisa Mapar ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Prognostic Information ◽  
Molecular Features ◽  
Increased Risk

Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, utilized machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can non-invasively guide treatment decisions.

scholarly journals Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Escudero ◽  
Anna Llort ◽  
Alexandra Arias ◽  
Ander Diaz-Navarro ◽  
Francisco Martínez-Ricarte ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Residual Disease ◽  
Tissue Sample ◽  
Secondary Effects ◽  
Diagnosis And Prognosis ◽  
Paediatric Brain Tumour ◽  
Ctdna Analysis ◽  
Disseminated Disease ◽  
Circulating Tumour Dna

Abstract The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. CSF ctDNA also characterises the intra-tumour genomic heterogeneity identifying small subclones. ctDNA is abundant in the CSF but barely present in plasma and longitudinal analysis of CSF ctDNA allows the study of minimal residual disease, genomic evolution and the characterisation of tumours at recurrence. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

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.

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