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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 -
Molecular Cancer Jan 2023Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are... (Review)
Review
Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.
Topics: Humans; Stomach Neoplasms; Liquid Biopsy; Biopsy; Prognosis; Neoplastic Cells, Circulating; DNA, Neoplasm; Biomarkers, Tumor
PubMed: 36627698
DOI: 10.1186/s12943-023-01715-z -
International Journal of Molecular... Jan 2023Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a... (Review)
Review
Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy-techniques, molecules, and sample type-for lung cancer.
Topics: Humans; Early Detection of Cancer; Biomarkers, Tumor; Lung Neoplasms; Liquid Biopsy; Cell-Free Nucleic Acids
PubMed: 36768828
DOI: 10.3390/ijms24032505 -
Molecular Cancer Feb 2022Alterations in DNAs could not reveal what happened in proteins. The accumulated alterations of DNAs would change the manifestation of proteins. Therefore, as is the case... (Review)
Review
Alterations in DNAs could not reveal what happened in proteins. The accumulated alterations of DNAs would change the manifestation of proteins. Therefore, as is the case in cancer liquid biopsies, deep proteome profiling will likely provide invaluable and clinically relevant information in real-time throughout all stages of cancer progression. However, due to the great complexity of proteomes in liquid biopsy samples and the limitations of proteomic technologies compared to high-plex sequencing technologies, proteomic discoveries have yet lagged behind their counterpart, genomic technologies. Therefore, novel protein technologies are in urgent demand to fulfill the goals set out for biomarker discovery in cancer liquid biopsies.Notably, conventional and innovative technologies are being rapidly developed for proteomic analysis in cancer liquid biopsies. These advances have greatly facilitated early detection, diagnosis, prognosis, and monitoring of cancer evolution, adapted or adopted in response to therapeutic interventions. In this paper, we review the high-plex proteomics technologies that are capable of measuring at least hundreds of proteins simultaneously from liquid biopsy samples, ranging from traditional technologies based on mass spectrometry (MS) and antibody/antigen arrays to innovative technologies based on aptamer, proximity extension assay (PEA), and reverse phase protein arrays (RPPA).
Topics: Early Detection of Cancer; Humans; Liquid Biopsy; Neoplasms; Proteome; Proteomics
PubMed: 35168611
DOI: 10.1186/s12943-022-01526-8 -
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 -
Annual Review of Analytical Chemistry... Jun 2022Cancer remains one of the leading causes of death, and early detection of this disease is crucial for increasing survival rates. Although cancer can be diagnosed... (Review)
Review
Cancer remains one of the leading causes of death, and early detection of this disease is crucial for increasing survival rates. Although cancer can be diagnosed following tissue biopsy, the biopsy procedure is invasive; liquid biopsy provides an alternative that is more comfortable for the patient. While blood, urine, and cerebral spinal fluid can all be used as a source of liquid biopsy, saliva is an ideal source of body fluid that is readily available and easily collected in the most noninvasive manner. Characterization of salivary constituents in the disease setting provides critical data for understanding pathophysiology and the evaluation of diagnostic potential. The aim of saliva diagnostics is therefore to develop a rapid and noninvasive detection of oral and systemic diseases that could be used together with compact analysis systems in the clinic to facilitate point-of-care diagnostics.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Humans; Liquid Biopsy; Neoplasms; Saliva
PubMed: 35696523
DOI: 10.1146/annurev-anchem-061020-123959 -
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 2022Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold... (Review)
Review
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Colorectal Neoplasms; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Prognosis
PubMed: 35337361
DOI: 10.1186/s12943-022-01556-2