scholarly journals Evolving Clinical Utility of Liquid Biopsy in Gastrointestinal Cancers

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1164 ◽  
Author(s):  
Jacobson ◽  
Munding ◽  
Hayden ◽  
Levy ◽  
Kuzel ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Clinical Evidence ◽  
Circulating Tumor Dna ◽  
Gastrointestinal Cancers ◽  
Liquid Biopsies ◽  
Colon And Rectum ◽  
Increased Sensitivity ◽  
Tumor Dna ◽  
Genomic Material

Room for improvement exists regarding recommendations for screening, staging, therapy selection, and frequency of surveillance of gastrointestinal cancers. Screening is costly and invasive, improved staging demands increased sensitivity and specificity to better guide therapy selection. Surveillance requires increased sensitivity for earlier detection and precise management of recurrences. Peripherally collected blood-based liquid biopsies enrich and analyze circulating tumor cells and/or somatic genomic material, including circulating tumor DNA along with various subclasses of RNA. Such assays have the potential to impact clinical practice at multiple stages of management in gastrointestinal cancers. This review summarizes current basic and clinical evidence for the utilization of liquid biopsy in cancers of the esophagus, pancreas, stomach, colon, and rectum. Technical aspects of various liquid biopsy methodologies and targets are reviewed and evidence supporting current commercially available assays is examined. Finally, current clinical applicability, potential future uses, and pitfalls of applying liquid biopsy to the screening, staging and therapeutic management of these diseases are discussed.

scholarly journals Liquid Biopsy in Gastrointestinal Cancers

Diagnostics ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 75 ◽  
Author(s):  
Aman Saini ◽  
Yash Pershad ◽  
Hassan Albadawi ◽  
Malia Kuo ◽  
Sadeer Alzubaidi ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Disease Surveillance ◽  
Biological Fluid ◽  
Genetic Material ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Gastrointestinal Cancers ◽  
New Paradigm ◽  
Liquid Biopsies ◽  
Biopsy Material

Liquid biopsy is the sampling of any biological fluid in an effort to enrich and analyze a tumor’s genetic material. Peripheral blood remains the most studied liquid biopsy material, with circulating tumor cells (CTC’s) and circulating tumor DNA (ctDNA) allowing the examination and longitudinal monitoring of a tumors genetic landscape. With applications in cancer screening, prognostic stratification, therapy selection and disease surveillance, liquid biopsy represents an exciting new paradigm in the field of cancer diagnostics and offers a less invasive and more comprehensive alternative to conventional tissue biopsy. Here, we examine liquid biopsies in gastrointestinal cancers, specifically colorectal, gastric, and pancreatic cancers, with an emphasis on applications in diagnostics, prognostics and therapeutics.

Circulating Tumor DNA: A Step into the Future of Cancer Management

2019 ◽  
Vol 63 (6) ◽  
pp. 456-465 ◽  
Author(s):  
Joana Fernandes Marques ◽  
Joana Pereira Reis ◽  
Gabriela Fernandes ◽  
Venceslau Hespanhol ◽  
José Carlos Machado ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
New Technologies ◽  
Therapy Response ◽  
Circulating Tumor Dna ◽  
Sample Collection ◽  
Cancer Management ◽  
The Past ◽  
Ctdna Analysis ◽  
Tumor Dna

Liquid biopsy was introduced to the oncology field with the promise of revolutionizing the management of cancer patients, minimizing the exposure to invasive procedures such as tissue biopsy, and providing reliable information regarding therapy response and detection of disease relapse. Despite the significant increase in the number of published studies on circulating tumor DNA (ctDNA) in the past years, the emphasis of most studies is on the development of new technologies or on the clinical utility of ctDNA. This leaves a clear gap of knowledge concerning the biology of ctDNA, such as the fundamental mechanisms through which DNA from tumor cells is released into the circulation. Moreover, considering that ctDNA analysis is now currently being applied in clinical practice, the need for rigorous quality control is arising, and with it the necessity to standardize procedures, from sample collection to data analysis. This review focuses on the main aspects of ctDNA, including approaches currently available to evaluate tumor genetics, as well as the points that still require improvement in order to make liquid biopsy a key player in precision medicine.

scholarly journals Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy

2020 ◽  
Vol 39 (3) ◽  
pp. 999-1013 ◽  
Author(s):  
Pieter A. Boonstra ◽  
Thijs T. Wind ◽  
Michel van Kruchten ◽  
Ed Schuuring ◽  
Geke A. P. Hospers ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Treatment Response ◽  
Clinical Utility ◽  
Tumor Response ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Liquid Biopsies ◽  
Secondary Resistance ◽  
Tumor Dna

Abstract Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed.

scholarly journals Extracellular Vesicle-Derived DNA vs. CfDNA as a Biomarker for the Detection of Colon Cancer

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1171
Author(s):  
Kavita Thakur ◽  
Manu Smriti Singh ◽  
Sara Feldstein-Davydova ◽  
Victoria Hannes ◽  
Dov Hershkovitz ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Mutation Detection ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
P Value ◽  
Liquid Biopsies ◽  
Targeted Ngs ◽  
Tumor Dna

Liquid biopsy has emerged as a promising non-invasive way to diagnose tumor and monitor its progression. Different types of liquid biopsies have different advantages and limitations. In the present research, we compared the use of two types of liquid biopsy, extracellular vesicle-derived DNA (EV-DNA) and cell-free DNA (cfDNA) for identifying tumor mutations in patients with colon carcinoma. Method: DNA was extracted from the tumor tissue of 33 patients diagnosed with colon carcinoma. Targeted NGS panel, based on the hotspots panel, was used to identify tumor mutations. Pre-surgery serum and plasma were taken from the patients in which mutation was found in the tumor tissue. Extracellular vesicles were isolated from the serum followed by the extraction of EV-DNA. CfDNA was extracted from the plasma. The mutations found in the tumor were used to detect the circulating tumor DNA using ultra-deep sequencing. We compared the sensitivity of mutation detection and allele frequency obtained in EV-DNA and cfDNA. Results: The sensitivity of mutation detection in EV-DNA and cfDNA was 61.90% and 66.67%, respectively. We obtained almost identical sensitivity of mutation detection in EV-DNA and cfDNA in each of the four stages of colon carcinoma. The total DNA concentration and number mutant copies were higher in cfDNA vs. EV-DNA (p value = 0.002 and 0.003, respectively). Conclusion: Both cfDNA and EV-DNA can serve as tumor biomarkers. The use of EV-DNA did not lead to improved sensitivity or better detection of tumor DNA in the circulation.

Greater than two coexisting mutations in KRAS and NRAS identified in the circulating tumor DNA fraction of liquid biopsies by NGS and confirmed with ddPCR.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15563-e15563
Author(s):  
Hala Boulos ◽  
Robert Tell ◽  
Nike Beaubier ◽  
Richard Blidner
Keyword(s):  
Liquid Biopsy ◽  
Detection Threshold ◽  
Treatment Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Precision Oncology ◽  
Single Nucleotide Variants ◽  
Liquid Biopsies ◽  
Low Frequencies ◽  
Tumor Dna

e15563 Background: Liquid biopsies are increasingly utilized as a non-invasive tool in precision oncology to assess tumor mutational profiles in order to select targeted therapies, detect treatment resistance, and monitor disease progression in cancer patients. Additionally, liquid biopsies may provide a more comprehensive representation of tumor heterogeneity than standard tissue biopsies. However, limitations such as scarcity of circulating tumor DNA (ctDNA) and/or variants at low frequencies can be technically challenging to detect by next-generation sequencing (NGS) assays. Here, we use NGS to detect greater than two KRAS/NRAS mutations coexisting in single samples at low variant allele frequencies (VAFs). Methods: The Tempus xF liquid biopsy NGS assay is designed to detect actionable oncologic targets spanning 105 genes in plasma. The assay was validated to reliably detect single-nucleotide variants at 0.25% VAF, indels and copy number variants at 0.5% VAF, and fusions at 1% VAF with 96.2%-100% specificity and 97.4%-100% sensitivity. Pre-designed digital PCR assays were modified to measure 10ng of cell-free DNA (cfDNA) on a droplet-digital PCR (ddPCR) platform. Results: Overall, we report 100% positive predictive value and high correlation between ddPCR results and xF VAF, as well as in individual variants, such as KRAS G12D. Unexpectedly, we detected more than two coexisting KRAS/NRAS mutations at a low VAF in the plasma samples. To orthogonally confirm these results, ddPCR was deployed to independently measure the presence of each cfDNA variant with a sensitivity of 0.09% VAF. Subsequent ddPCR analysis of all targeted variants were concordant with NGS results. Conclusions: The occurrence of multiple KRAS and NRAS mutations in a single sample is quite uncommon and may be falsely interpreted as an NGS artifact. However, verification of this phenomenon by ddPCR confirmed the validity of the NGS liquid biopsy approach. These results highlight the capability of the Tempus xF assay to detect low-frequency variants, including those that fall below the validated detection threshold, which is essential for the diagnosis of early disease.

scholarly journals Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7651
Author(s):  
Miles W. Grunvald ◽  
Richard A. Jacobson ◽  
Timothy M. Kuzel ◽  
Sam G. Pappas ◽  
Ashiq Masood
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Standard Care ◽  
Clinical Utility ◽  
Circulating Tumor Dna ◽  
Current Status ◽  
Free Dna ◽  
Tumor Dna ◽  
Active Investigation

Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians. In this publication, we aim to review cfDNA liquid biopsy in pancreatic cancer with an emphasis on current techniques, clinical utility, and areas of active investigation. We feel that researchers and clinicians alike should be familiar with this exciting modality as it gains increasing importance in the care of cancer patients.

scholarly journals Translational Utility of Liquid Biopsies in Thyroid Cancer Management

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3443
Author(s):  
Ayanthi A. Wijewardene ◽  
Marthe Chehade ◽  
Matti L. Gild ◽  
Roderick J. Clifton-Bligh ◽  
Martyn Bullock
Keyword(s):  
Thyroid Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Liquid Biopsies ◽  
Future Directions ◽  
Cancer Management ◽  
Diagnostic Role ◽  
Tumor Dna

Liquid biopsies are a novel technique to assess for either circulating tumor cells (CTC) or circulating tumor DNA (ctDNA and microRNA (miRNA)) in peripheral blood samples of cancer patients. The diagnostic role of liquid biopsy in oncology has expanded in recent years, particularly in lung, colorectal and breast cancer. In thyroid cancer, the role of liquid biopsy in either diagnosis or prognosis is beginning to translate from the lab to the clinic. In this review, we describe the evolution of liquid biopsies in detecting CTC, ctDNA and miRNA in thyroid cancer patients, together with its limitations and future directions in clinical practice.

scholarly journals Perspectives of the Application of Liquid Biopsy in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Yuhan Ding ◽  
Wenxia Li ◽  
Kun Wang ◽  
Chang Xu ◽  
Mengdi Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liquid Biopsy ◽  
Management Strategies ◽  
Circulating Tumor Dna ◽  
Liquid Biopsies ◽  
Current Management ◽  
Noninvasive Methods ◽  
Noninvasive Biomarker ◽  
Treatment Responses ◽  
Tumor Dna

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors and the second leading cause of cancer death worldwide. Since traditional biopsies are invasive and do not reflect tumor heterogeneity or monitor the dynamic progression of tumors, there is an urgent need for new noninvasive methods that can supplement and improve the current management strategies of CRC. Blood-based liquid biopsies are a promising noninvasive biomarker that can detect disease early, assist in staging, monitor treatment responses, and predict relapse and metastasis. Over time, an increasing number of experiments have indicated the clinical utility of liquid biopsies in CRC. In this review, we mainly focus on the development of circulating tumor cells and circulating tumor DNA as key components of liquid biopsies in CRC and introduce the potential of exosomal microRNAs as emerging liquid biopsy markers in clinical application for CRC.

scholarly journals Role of Circulating Tumor DNA in Hematological Malignancy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2078
Author(s):  
Miho Ogawa ◽  
Kazuaki Yokoyama ◽  
Seiya Imoto ◽  
Arinobu Tojo
Keyword(s):  
Liquid Biopsy ◽  
Hematological Malignancies ◽  
Residual Disease ◽  
Current Knowledge ◽  
Circulating Tumor Dna ◽  
Liquid Biopsies ◽  
Recent Advances ◽  
Minimal Residual Disease Monitoring ◽  
Tumor Dna

With the recent advances in noninvasive approaches for cancer diagnosis and surveillance, the term “liquid biopsy” has become more familiar to clinicians, including hematologists. Liquid biopsy provides a variety of clinically useful genetic data. In this era of personalized medicine, genetic information is critical to early diagnosis, aiding risk stratification, directing therapeutic options, and monitoring disease relapse. The validity of circulating tumor DNA (ctDNA)-mediated liquid biopsies has received increasing attention. This review summarizes the current knowledge of liquid biopsy ctDNA in hematological malignancies, focusing on the feasibility, limitations, and key areas of clinical application. We also highlight recent advances in the minimal residual disease monitoring of leukemia using ctDNA. This article will be useful to those involved in the clinical practice of hematopoietic oncology.

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