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 Liquid Biopsy in Melanoma: Significance in Diagnostics, Prediction and Treatment Monitoring

2021 ◽  
Vol 22 (18) ◽  
pp. 9714
Author(s):  
Paula Kamińska ◽  
Karolina Buszka ◽  
Maciej Zabel ◽  
Michał Nowicki ◽  
Catherine Alix-Panabières ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Treatment Monitoring ◽  
Cancer Diagnostics ◽  
Continuous Control ◽  
Patient Stratification ◽  
Sample Collection ◽  
Common Term ◽  
Tumor Dna ◽  
Selection Of

Liquid biopsy is a common term referring to circulating tumor cells and other biomarkers, such as circulating tumor DNA (ctDNA) or extracellular vesicles. Liquid biopsy presents a range of clinical advantages, such as the low invasiveness of the blood sample collection and continuous control of the tumor progression. In addition, this approach enables the mechanisms of drug resistance to be determined in various methods of cancer treatment, including immunotherapy. However, in the case of melanoma, the application of liquid biopsy in patient stratification and therapy needs further investigation. This review attempts to collect all of the relevant and recent information about circulating melanoma cells (CMCs) related to the context of malignant melanoma and immunotherapy. Furthermore, the biology of liquid biopsy analytes, including CMCs, ctDNA, mRNA and exosomes, as well as techniques for their detection and isolation, are also described. The available data support the notion that thoughtful selection of biomarkers and technologies for their detection can contribute to the development of precision medicine by increasing the efficacy of cancer diagnostics and treatment.

Circulating tumor DNA analysis of genomic alterations in metastatic urothelial carcinoma from NCT03113266 study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 486-486
Author(s):  
Haige Chen ◽  
Ruiyun Zhang ◽  
Feng Xie ◽  
Pan Du ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Genomic Alterations ◽  
Invasive Approach ◽  
Synonymous Mutations ◽  
Therapeutic Decisions ◽  
Metastatic Urothelial Carcinoma ◽  
Ctdna Analysis ◽  
Tumor Dna

486 Background: Recent studies have suggested the predictive value of liquid biopsies for immune checkpoint inhibitors. NCT03113266 is a multicenter phase II trial to evaluate the safety and efficacy of toripalimab (anti-PD-1) in metastatic urothelial carcinoma (mUC). Here we report the initial circulating tumor DNA (ctDNA) analysis of genomic alterations from a single-institution biomarker cohort. Methods: Twenty-seven mUC patients receiving toripalimab (3 mg/kg Q2W) at Ren Ji Hospital were enrolled and consented to Institutional Review Board-approved protocols permitting biomaterial collection and genetic sequencing. Serial plasma specimens were obtained at baseline and every two cycles. The 600-gene panel (PredicineATLAS) liquid biopsy assay was applied to assess somatic variants and blood tumor mutational burden (bTMB). Results: The ctDNA assays were performed successfully for 100% of baseline samples (n = 27) with average read depth of 24,389 (range 14,000-31,700). A total of 571 non-synonymous mutations were identified, demonstrating prevalent aberrations in TP53 (63%), TERT promoter (30%), KDM2D (26%), PPM1D (26%), and KDM6A (26%). In 5 patients, FGFR3 variants were detected, including 6 missense sites and 4 FGFR3- TACC3 fusion events. Copy number gain ( FGFR1, ERBB2) and loss ( PTEN, BRCA2, CDKN2A) were pinpointed. TMB estimation revealed one case with an exceptionally high bTMB (62.6 mutations/Mb) and genomic features of microsatellite instability (MSI). Concordance with tumor-based genotyping and ctDNA kinetics during toripalimab treatment are being determined. Conclusions: Prospective ctDNA analysis using the PredicineATLAS liquid biopsy assay is feasible and represents a minimally invasive approach to detecting cancer-specific genetic landscape and potentially guiding personalized therapeutic decisions in mUC patients. Clinical trial information: NCT03113266 . Research Sponsor: Shanghai Junshi BioSciences; Huidu Shanghai Medical Sciences Ltd

scholarly journals Capturing Genomic Evolution of Lung Cancers through Liquid Biopsy for Circulating Tumor DNA

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Michael Offin ◽  
Jacob J. Chabon ◽  
Pedram Razavi ◽  
James M. Isbell ◽  
Charles M. Rudin ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Intratumoral Heterogeneity ◽  
Darwinian Evolution ◽  
Genomic Evolution ◽  
Current Standard ◽  
Genetic Sequencing ◽  
Lung Cancers ◽  
Ctdna Analysis ◽  
Tumor Dna

Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor’s dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA) analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure. The ability to analyze ctDNA from plasma, CSF, or urine enables a comprehensive view of cancers as systemic diseases and captures intratumoral heterogeneity. Here, we describe these recent advances in the setting of lung cancers and advocate for further research and the incorporation of ctDNA analysis in clinical trials of targeted therapies. By capturing genomic evolution in a noninvasive manner, liquid biopsy for ctDNA analysis could accelerate therapeutic discovery and deliver the next leap forward in precision medicine for patients with lung cancers and other solid tumors.

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.

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

2018 ◽  
Vol 56 (2) ◽  
pp. 186-197 ◽  
Author(s):  
Lydia Giannopoulou ◽  
Sabine Kasimir-Bauer ◽  
Evi S. Lianidou
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Sample Collection ◽  
Clinical Value ◽  
Solid Malignancies ◽  
Tumor Dna ◽  
Shed Light

Abstract Ovarian cancer remains the most lethal disease among gynecological malignancies despite the plethora of research studies during the last decades. The majority of patients are diagnosed in an advanced stage and exhibit resistance to standard chemotherapy. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) represent the main liquid biopsy approaches that offer a minimally invasive sample collection. Both have shown a diagnostic, prognostic and predictive value in many types of solid malignancies and recent studies attempted to shed light on their role in ovarian cancer. This review is mainly focused on the clinical value of both CTCs and ctDNA in ovarian cancer and, more specifically, on their potential as diagnostic, prognostic and predictive tumor biomarkers.

scholarly journals Future perspectives of circulating tumor DNA in colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770574 ◽  
Author(s):  
C Nadal ◽  
T Winder ◽  
A Gerger ◽  
David Tougeron
Keyword(s):  
Colorectal Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Genetic Material ◽  
Treatment Resistance ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Response Monitoring ◽  
Cancer Management ◽  
Tumor Dna

Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

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.

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