scholarly journals The Translational Status of Cancer Liquid Biopsies

2019 ◽  
Author(s):  
Sinisa Bratulic ◽  
Francesco Gatto ◽  
Jens Nielsen
Keyword(s):  
Treatment Outcomes ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Biomarker Research ◽  
Successes And Challenges

Abstract Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research.

scholarly journals The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yunjing Zhang ◽  
Ying Wang ◽  
Xinwan Su ◽  
Ping Wang ◽  
Weiqiang Lin
Keyword(s):  
Liquid Biopsy ◽  
Screening Tool ◽  
Clinical Medicine ◽  
High Specificity ◽  
Circular Rna ◽  
Body Fluids ◽  
Precision Oncology ◽  
Clinical Practices ◽  
Non Invasive ◽  
Human Cancers

Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of current invasive tissue examinations in precision oncology. Circular RNA (circRNA) is a recent, novel, and attractive liquid biomarker showing stability, abundance, and high specificity in various diseases, especially in human cancers. This review focused on the emerging potential of human circRNA in body fluids as the liquid biopsy biomarkers for cancers and the methods used to detect the circRNA expression and summarized the construction of circRNA biomarkers in body fluids for treating human cancers and their limitations before they become part of routine clinical medicine. Furthermore, the future opportunities and challenges of translating circRNAs in liquid biopsy into clinical practices were explored.

Liquid Biopsy beyond Circulating Tumor Cells and Cell-Free DNA

2019 ◽  
Vol 63 (6) ◽  
pp. 479-488 ◽  
Author(s):  
Susana Junqueira-Neto ◽  
Inês A. Batista ◽  
José Luís Costa ◽  
Sónia A. Melo
Keyword(s):  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Great Promise ◽  
Genetic Profile ◽  
Clonal Heterogeneity ◽  
Surgical Biopsy ◽  
Non Invasive ◽  
Metastatic Lesions ◽  
Detection Tool

Liquid biopsy represents the analysis of tumor-derived material in the blood and other body fluids of cancer patients. This portrays a minimally invasive detection tool for molecular biomarkers. Liquid biopsy has emerged as a complementary or alternative method to surgical biopsy. This non-invasive detection tool overcomes the recurrent problems in the clinical assessment of tumors that stem from the lack of accessibility to the tumor tissue and its clonal heterogeneity. Moreover, body fluid-derived components have shown to reflect the genetic profile of both primary and metastatic lesions and provide a real-time monitoring of tumor dynamics, representing a great promise for personalized medicine. This review will highlight the latest breakthroughs and the current applications of several tumor-derived biomarkers that can be found in body fluids. The authors will focus on tumor-derived exosomes, tumor-educated platelets, and circulating tumor miRNAs and mRNAs, and how these can be used for tumor detection.

scholarly journals Exosomes: A Forthcoming Era of Breast Cancer Therapeutics

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4672
Author(s):  
Banashree Bondhopadhyay ◽  
Sandeep Sisodiya ◽  
Faisal Abdulrahman Alzahrani ◽  
Muhammed A. Bakhrebah ◽  
Atul Chikara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Breast Cancer Patients ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Circulating Markers

Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

scholarly journals Detecting an ALK Rearrangement via Liquid Biopsy Enabled a Targeted Therapy-based Approach for Treating a Patient with Advanced Non-small Cell Lung Cancer

2018 ◽  
Vol 14 (1) ◽  
pp. 38 ◽  
Author(s):  
Alejandro R Calvo ◽  
Gabriel H Ibarra ◽  
Cecile Rose T Vibat ◽  
Veena M Singh
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
Molecular Testing ◽  
Tissue Analysis ◽  
Alk Rearrangement ◽  
Blood Draw ◽  
Diagnostic Biopsy

Initial diagnostic biopsy procedures often yield insufficient tissue for molecular testing, and invasive surgical biopsies can be associated with significant cost as well as risk to the patient. Liquid biopsy offers an alternative and economical means for molecular characterization of tumors via a simple peripheral blood draw. This case report describes the ability of liquid biopsy to detect an ALK translocation where tissue analysis by fluorescence in situ hybridization was negative for the genetic alteration. Identification of an ALK rearrangement in circulating tumor cells from a blood specimen led to sequential targeted therapies that included crizotinib followed by alectinib. The patient demonstrated outstanding clinical response during treatment with each of the prescribed ALK inhibitors. This case demonstrates the clinical utility of Biocept’s liquid biopsy to detect actionable biomarkers by surveying the systemic landscape of a patient’s disease where identification of the same genetic drivers may be missed in analyses of heterogeneous tumor tissue.

Multi-analyte liquid biopsies based treatment in advanced refractory cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15623-e15623
Author(s):  
Sewanti Limaye ◽  
Darshana Patil ◽  
Dadasaheb B Akolkar ◽  
Timothy Crook ◽  
Anantbhushan Ranade ◽  
...  
Keyword(s):  
Treatment Response ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Single Gene ◽  
Objective Response ◽  
Specific Treatment ◽  
Patient Specific ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Blood Draw

e15623 Background: Tumor tissue profiling following invasive biopsies is presently the standard approach for indication-based therapy management in solid organ cancers. However, challenges in biopsy are traditionally described due to proximity to vital organs, or patients’ co-morbidities or unwillingness for an invasive procedure. Liquid biopsies for evaluation of cancers are also largely restricted to single gene testing for selection of targeted therapy agents. We developed a comprehensive liquid biopsy based multi-analyte (molecular and functional) investigation of the cancer (eLBx: Encyclopedic Liquid Biopsy) for selection and management of individualised treatments in a cohort of advanced refractory cancers. Methods: We obtained 20 mL blood from 65 patients with solid organ cancers where the disease had progressed following failure of at least two lines of systemic therapies and where biopsy to obtain tumor tissue for molecular profiling of tumor was unviable. Cell free tumor DNA (ctDNA) was interrogated for mutations, while exosomal mRNA was profiled for gene expression. Viable circulating tumor associated cells (C-TACs) were tested in vitro for chemoresistance and used to determine expression of cell surface signalling receptors by immunocytochemistry (ICC). The findings were integrated to generate patient-specific treatment regimens. In patients who received treatment, response was determined radiologically. Results: Fifty-one patients received eLBx-guided personalized treatments with combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Forty-three patients were evaluable for treatment response per protocol among whom Partial Response (PR) was observed in 14 patients yielding an Objective Response Rate (ORR) of 32.6%. Additionally, 23 patients showed Stable Disease thus yielding an overall Disease Control rate of 86.1%. Median Progression Free Survival (PFS) was 108 days. There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: The ability to make informed treatment choices from a convenient blood draw implies a reduced dependence on invasive biopsies for disease management. We demonstrate successful management of advanced refractory solid tumor malignancies using an integrational non-invasive multi-analyte liquid biopsy approach. Clinical trial information: CTRI/2019/02/017548.

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.

Incidence of Androgen Receptor and DNA Repair Gene Mutations in Advanced Solid Malignancies: Clinical Impact of Liquid Biopsy at Veteran Affairs Medical Center

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S145-S146
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
Dna Repair ◽  
Liquid Biopsy ◽  
Medical Center ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Repair Gene ◽  
Solid Malignancies ◽  
Dna Repair Gene

Abstract Introduction/Objective The advent of Liquid biopsy targeting genetic mutations in solid tumors is a major milestone in field of precision oncology. This minimally invasive, novel revolutionary technique analyses circulating tumor cells (CTC) in peripheral blood and detects signature genomic alterations. DNA repair gene (DDR) mutations have been reported in 25-40% of prostatic cancers and >50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers. One of the DDR, especially Tp53 has been found to be associated with poor prognosis and increased germline mutations. We herein present a quality assurance study to determine feasibility of liquid biopsy for personalized management in veterans for advanced solid malignancies and its clinical impact. Methods Quality assurance documentation from Foundation One (Cambridge MA, NGS) on liquid biopsies performed for the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) from May 2019 to April 15, 2020 were reviewed. Statistical data for adequacy, cases with notable mutations, frequency and type of mutations of AR, DNA damage repair (DDR) gene and Tp53 were noted. Results A total of 31 liquid biopsies were performed over this time period, of which 29/31 (93.50%) were adequate for evaluation. 23/29 (79.30%) showed notable mutations, in 4/23 (17.39%) guided treatment decisions based on androgen receptor (AR) amplification, and 7/29 (24.1%) of all cases showed DDR gene mutations indicating poor outcome and resistance to the current therapy. Greater than 50% (16/29 (55.7%)) of the veterans with advanced cancers harbored Tp53 mutation, which instills hope and future insight for patient tailored oncologic therapy. Conclusion The minimally invasive liquid biopsy shows a great promise as a diagnostic and prognostic tool in the personalized clinical management of advanced prostate and NSCLC in veteran patient population with unique demographic characteristics. Difference in frequency of the genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 in future for personalized targeted therapy.

scholarly journals Liquid biopsy for patients with IBD-associated neoplasia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hideaki Kinugasa ◽  
Sakiko Hiraoka ◽  
Kazuhiro Nouso ◽  
Shumpei Yamamoto ◽  
Mami Hirai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Target Genes ◽  
Tumor Tissue ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Inflammatory Bowel

Abstract Background It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

Total microfluidic platform strategy for liquid biopsy

2020 ◽  
pp. 1-25
Author(s):  
Sehyun Shin
Keyword(s):  
Liquid Biopsy ◽  
Residual Disease ◽  
Future Research ◽  
Microfluidic Platforms ◽  
Liquid Biopsies ◽  
Related Area ◽  
Detailed Review ◽  
Non Invasive ◽  
Clinical Benefits ◽  
Minimal Residual

A liquid biopsy is a simple and non-invasive biopsy that examines a range of information about a tumor through a simple blood sample. Due to its non-invasive nature, liquid biopsy has many outstanding clinical benefits, including repetitive sampling and examination, representation of whole mutations, observation of minimal residual disease etc. However, liquid biopsy requires various processes such as sample preparation, amplification, and target detection. These processes can be integrated onto microfluidic platforms, which may provide a sample-to-answer system. The present review provides a brief overview of liquid biopsies, a detailed review of the technologies in each process, and prospective concluding remarks. Through this review, one can have a basic but cross-disciplinary understanding of liquid biopsy, as well as knowledge of new starting points for future research in each related area.

scholarly journals Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4500
Author(s):  
Isabel Heidrich ◽  
Thaer S. A. Abdalla ◽  
Matthias Reeh ◽  
Klaus Pantel
Keyword(s):  
Colorectal Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Personalized Therapy ◽  
Liquid Biopsies ◽  
Curative Surgery ◽  
Non Invasive ◽  
Staging Systems

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is a heterogeneous tumor with a wide genomic instability, leading to tumor recurrence, distant metastasis, and therapy resistance. Therefore, adjunct non-invasive tools are urgently needed to help the current classical staging systems for more accurate prognostication and guiding personalized therapy. In recent decades, there has been an increasing interest in the diagnostic, prognostic, and predictive value of circulating cancer-derived material in CRC. Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA. We will discuss some of the advantages and limitations of LBs and the future perspectives in the field of CRC management.

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