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Journal of Hematology & Oncology Sep 2022Liquid biopsies are increasingly used for cancer molecular profiling that enables a precision oncology approach. Circulating extracellular nucleic acids (cell-free DNA;... (Review)
Review
Liquid biopsies are increasingly used for cancer molecular profiling that enables a precision oncology approach. Circulating extracellular nucleic acids (cell-free DNA; cfDNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) can be isolated from the blood and other body fluids. This review will focus on current technologies and clinical applications for liquid biopsies. ctDNA/cfDNA has been isolated and analyzed using many techniques, e.g., droplet digital polymerase chain reaction, beads, emulsion, amplification, and magnetics (BEAMing), tagged-amplicon deep sequencing (TAm-Seq), cancer personalized profiling by deep sequencing (CAPP-Seq), whole genome bisulfite sequencing (WGBS-Seq), whole exome sequencing (WES), and whole genome sequencing (WGS). CTCs have been isolated using biomarker-based cell capture, and positive or negative enrichment based on biophysical and other properties. ctDNA/cfDNA and CTCs are being exploited in a variety of clinical applications: differentiating unique immune checkpoint blockade response patterns using serial samples; predicting immune checkpoint blockade response based on baseline liquid biopsy characteristics; predicting response and resistance to targeted therapy and chemotherapy as well as immunotherapy, including CAR-T cells, based on serial sampling; assessing shed DNA from multiple metastatic sites; assessing potentially actionable alterations; analyzing prognosis and tumor burden, including after surgery; interrogating difficult-to biopsy tumors; and detecting cancer at early stages. The latter can be limited by the small amounts of tumor-derived components shed into the circulation; furthermore, cfDNA assessment in all cancers can be confounded by clonal hematopoeisis of indeterminate potential, especially in the elderly. CTCs can be technically more difficult to isolate that cfDNA, but permit functional assays, as well as evaluation of CTC-derived DNA, RNA and proteins, including single-cell analysis. Blood biopsies are less invasive than tissue biopsies and hence amenable to serial collection, which can provide critical molecular information in real time. In conclusion, liquid biopsy is a powerful tool, and remarkable advances in this technology have impacted multiple aspects of precision oncology, from early diagnosis to management of refractory metastatic disease. Future research may focus on fluids beyond blood, such as ascites, effusions, urine, and cerebrospinal fluid, as well as methylation patterns and elements such as exosomes.
Topics: Aged; Cell-Free Nucleic Acids; Circulating Tumor DNA; Humans; Immune Checkpoint Inhibitors; Liquid Biopsy; Neoplastic Cells, Circulating; Precision Medicine; Technology
PubMed: 36096847
DOI: 10.1186/s13045-022-01351-y -
Molecular Cancer Jan 2022Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so... (Review)
Review
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
Topics: Animals; Biomarkers, Tumor; Circulating Tumor DNA; Clinical Decision-Making; Disease Management; Disease Susceptibility; Exosomes; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Lung Neoplasms; Neoplastic Cells, Circulating; Prognosis
PubMed: 35057806
DOI: 10.1186/s12943-022-01505-z -
Molecular Cancer Feb 2022Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer... (Review)
Review
Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer diagnosis and prognosis prediction. Exosomes are a subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient cells and play a crucial role in mediating intercellular communication. Increasing studies suggest that exosomes have a great promise to serve as novel biomarkers in liquid biopsy, since large quantities of exosomes are enriched in body fluids and are involved in numerous physiological and pathological processes. However, the further clinical application of exosomes has been greatly restrained by the lack of high-quality separation and component analysis methods. This review aims to provide a comprehensive overview on the conventional and novel technologies for exosome isolation, characterization and content detection. Additionally, the roles of exosomes serving as potential biomarkers in liquid biopsy for the diagnosis, treatment monitoring, and prognosis prediction of cancer are summarized. Finally, the prospects and challenges of applying exosome-based liquid biopsy to precision medicine are evaluated.
Topics: Biomarkers, Tumor; Exosomes; Humans; Liquid Biopsy; Neoplasms; Precision Medicine; Prognosis
PubMed: 35180868
DOI: 10.1186/s12943-022-01509-9 -
Acta Cytologica 2019Liquid biopsy provides the opportunity of detecting, analyzing and monitoring cancer in various body effluents such as blood or urine instead of a fragment of cancer... (Review)
Review
Liquid biopsy provides the opportunity of detecting, analyzing and monitoring cancer in various body effluents such as blood or urine instead of a fragment of cancer tissue. It is composed of different biological matrices such as circulating tumor cells (CTCs), cell free nucleic acids, exosomes or tumors "educated platelets." In addition to representing a non- or minimally invasive procedure, it should represent a better view of tumor heterogeneity and allows for real-time monitoring of cancer evolution. Recent technological and molecular advances, greatly facilitated by the use of microfluidics in many cases, have permitted large progresses both in our ability to purify and analyze liquid biopsy components. In particular, the great developments of droplet-based digital PCR and the various optimizations of next generation sequencing technologies are central to the several validations of CTC-free DNA as a strong cancer biomarker. However, complete adoption of liquid biopsy in clinics will require pursuing recent efforts in the standardization of procedures both on the pre-analytical and analytical aspects.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Biopsy, Fine-Needle; Cell-Free Nucleic Acids; Circulating Tumor DNA; Exosomes; Humans; Liquid Biopsy; Monitoring, Physiologic; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Cells, Circulating
PubMed: 31091522
DOI: 10.1159/000499337 -
Cancer Discovery Apr 2021Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational... (Review)
Review
Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational research. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with promising first results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Here, we propose a conceptual framework of CTC and ctDNA assays and point out current challenges of CTC and ctDNA research, which might structure this dynamic field of translational cancer research. SIGNIFICANCE: The analysis of blood for CTCs or cell-free nucleic acids called "liquid biopsy" has opened new avenues for cancer diagnostics, including early detection of tumors, improved risk assessment and staging, as well as early detection of relapse and monitoring of tumor evolution in the context of cancer therapies.
Topics: Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neoplasms
PubMed: 33811121
DOI: 10.1158/2159-8290.CD-20-1311 -
Cells Jul 2023The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues... (Review)
Review
The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, the surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumours, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.
Topics: Humans; Liquid Biopsy; Cell-Free Nucleic Acids; MicroRNAs; Central Nervous System Neoplasms; Biomarkers
PubMed: 37508574
DOI: 10.3390/cells12141911 -
Human Genomics Aug 2019In recent years, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost with improved accuracy. In... (Review)
Review
In recent years, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost with improved accuracy. In the area of liquid biopsy, NGS has been applied to sequence circulating tumor DNA (ctDNA). Since ctDNA is the DNA fragments released by tumor cells, it can provide a molecular profile of cancer. Liquid biopsy can be applied to all stages of cancer diagnosis and treatment, allowing non-invasive and real-time monitoring of disease development. The most promising aspects of liquid biopsy in cancer applications are cancer screening and early diagnosis because they can lead to better survival results and less disease burden. Although many ctDNA sequencing methods have enough sensitivity to detect extremely low levels of mutation frequency at the early stage of cancer, how to effectively implement them in population screening settings remains challenging. This paper focuses on the application of liquid biopsy in the early screening and diagnosis of cancer, introduces NGS-related methods, reviews recent progress, summarizes challenges, and discusses future research directions.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Early Detection of Cancer; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Neoplasms
PubMed: 31370908
DOI: 10.1186/s40246-019-0220-8 -
Cell Death & Disease Oct 2022Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor... (Review)
Review
Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.
Topics: Humans; Stomach Neoplasms; Prognosis; Liquid Biopsy; Circulating Tumor DNA; Neoplastic Cells, Circulating; Biomarkers, Tumor
PubMed: 36302755
DOI: 10.1038/s41419-022-05350-2 -
International Journal of Molecular... Sep 2022Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the... (Review)
Review
Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.
Topics: Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Female; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating
PubMed: 36077348
DOI: 10.3390/ijms23179952 -
Molecular Cancer Mar 2022Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies... (Review)
Review
Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.
Topics: Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Prognosis; Proteomics
PubMed: 35303879
DOI: 10.1186/s12943-022-01543-7