scholarly journals Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1251 ◽  
Author(s):  
Tuaeva ◽  
Falzone ◽  
Porozov ◽  
Nosyrev ◽  
Trukhan ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Liquid Biopsy ◽  
Prognostic Significance ◽  
Circulating Tumor Dna ◽  
Molecular Techniques ◽  
Unknown Primary ◽  
Diagnostic Strategies ◽  
Early Diagnosis Of Cancer ◽  
Mutational Status ◽  
Ctdna Analysis

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients’ prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients’ samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.

Kras-Diagnosing the Little-Known Cancers Oncogene through Liquid Biopsy: Review

2020 ◽  
Author(s):  
Hafiz Syed Mohammad Osama Jafri
Keyword(s):  
Liquid Biopsy ◽  
Prognostic Significance ◽  
Cost Effective ◽  
Circulating Tumor Dna ◽  
Cancer Therapies ◽  
Oncogenic Signaling ◽  
Quick Method ◽  
Downstream Signaling ◽  
Mutational Status ◽  
Initial Stage

Tissue biopsy, until date, is a gold standard for tumor diagnosis, grading, treatment, and detecting genetic evidences for identifying appropriate personalized treatments. However, it is painful, invasive, expensive, and risky making sequential biopsies basically impractical. Detection of Kras genes through liquid biopsy is the growing theragnostic technique, which is more sensitive, specific, much cost-effective and quick method for detecting the mutational status of cancers. Liquid biopsy detects biomarkers present in various body fluids, such as plasma, urine, saliva and cerebrospinal fluid, harboring cancer degraded fragments and cells shed by carcinoma such as circulating tumor cells, microRNA and circulating tumor DNA. It can be utilized as a pre-screening test for initial stage cancers also where multiple sampling is required for monitoring cancer therapies. Kras is the most extensively mutated cancer oncogene involve in altering the downstream signaling pathways, increasing oncogenic signaling, which is typically associated with poor prognosis and resistance to therapy. This review was conducted to clarify its prognostic significance as well as its mutational role in different carcinomas. To identify studies related to Kras mutation Medline, PubMed, Google Scholar and Web of Science search engines were explored and forty two relevant researches were finalized from year 2005 to 2019.

scholarly journals On-Chip Liquid Biopsy: Progress in Isolation of Exosomes for Early Diagnosis of Cancer

2017 ◽  
Vol 112 (3) ◽  
pp. 461a ◽  
Author(s):  
Sung Cheol Kim ◽  
Navneet Dogra ◽  
Benjamin H. Wunsch ◽  
Joshua T. Smith ◽  
Stacey M. Gifford ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Liquid Biopsy ◽  
Early Diagnosis Of Cancer ◽  
Diagnosis Of Cancer ◽  
On Chip

scholarly journals Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Qing Yin ◽  
Chun-Hui Yuan ◽  
Zhen Qu ◽  
Qing Guan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Prognostic Significance ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Diagnostic Strategies ◽  
Systemic Treatments

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.

scholarly journals The prospect of using liquid biopsy in diagnosis and treatment strategy in patients with carcinomas of unknown primary

2021 ◽  
Vol 7 (4) ◽  
pp. 10-19
Author(s):  
I. B. Kononenko ◽  
M. G. Filippova ◽  
A. V. Snegovoy ◽  
S. L. Gutorov
Keyword(s):  
Tumor Cells ◽  
Liquid Biopsy ◽  
Tissue Specificity ◽  
Circulating Tumor Dna ◽  
Patient Treatment ◽  
Unknown Primary ◽  
Molecular Characteristics ◽  
Scientific Databases ◽  
Circulating Free Dna ◽  
Personalized Approach

Background. The search and use of new molecular prognostic and predictive markers of efficacy detected by liquid biopsy are aimed at understanding the biology of Carcinomas of Unknown Primary (CUP) and improving results of patient treatment. The review is devoted to advances in scientific and clinical research on this issue.Materials and methods. In order to assess the current state of the problem, a search and analysis of relevant data of the scientific databases PubMed, Medline, RISC was carried out.Results. The scientific rationale for the use of liquid biopsy in clinical practice to improve the treatment of cancer patients with CUP is presented. The results of the use of modern approaches to the analysis of fluid biopsy samples in CUP are presented. In particular, the features of using circulating free DNA, circulating tumor DNA, circulating tumor cells in the analysis are considered. The modern possibilities of determining tissue specificity using liquid biopsy in CUP are discussed. The prospects for the development of liquid biopsy for improving diagnostics, determining the prognosis of the disease, and choosing a strategy for treating CUP and the treatment monitoring have been determined.Conclusion. A review of the literature confirms that modern methods of molecular profiling of tumor cells obtained both as a result of liquid biopsy and tissue biopsies will make a significant contribution to the determination of tissue specificity, molecular characteristics of CUP for a personalized approach in order to improve strategies and treatment outcomes for patients with CUP.

scholarly journals A Multicenter Study to Assess EGFR Mutational Status in Plasma: Focus on an Optimized Workflow for Liquid Biopsy in a Clinical Setting

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 290 ◽  
Author(s):  
Laure Sorber ◽  
Karen Zwaenepoel ◽  
Koen De Winne ◽  
Kaat Van Casteren ◽  
Elien Augustus ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Transit Time ◽  
Multicenter Study ◽  
Clinical Setting ◽  
Liquid Biopsy ◽  
High Speed ◽  
Mutational Analysis ◽  
Mutational Status ◽  
Ctdna Analysis ◽  
Gdna Contamination

A multicenter study was performed to determine an optimal workflow for liquid biopsy in a clinical setting. In total, 549 plasma samples from 234 non-small cell lung cancer (NSCLC) patients were collected. Epidermal Growth Factor Receptor (EGFR) circulating cell-free tumor DNA (ctDNA) mutational analysis was performed using digital droplet PCR (ddPCR). The influence of (pre-) analytical variables on ctDNA analysis was investigated. Sensitivity of ctDNA analysis was influenced by an interplay between increased plasma volume (p < 0.001) and short transit time (p = 0.018). Multistep, high-speed centrifugation both increased plasma generation (p < 0.001) and reduced genomic DNA (gDNA) contamination. Longer transit time increased the risk of hemolysis (p < 0.001) and low temperatures were shown to have a negative effect. Metastatic sites were found to be strongly associated with ctDNA detection (p < 0.001), as well as allele frequency (p = 0.034). Activating mutations were detected in a higher concentration and allele frequency compared to the T790M mutation (p = 0.003, and p = 0.002, respectively). Optimization of (pre-) analytical variables is key to successful ctDNA analysis. Sufficient plasma volumes without hemolysis or gDNA contamination can be achieved by using multistep, high-speed centrifugation, coupled with short transit time and temperature regulation. Metastatic site location influenced ctDNA detection. Finally, ctDNA levels might have further value in detecting resistance mechanisms.

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.

Massively parallel sequencing (MPS) of circulating DNA in patients with metastatic colorectal cancer (mCRC): Prognostic significance and early changes during chemotherapy (CT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11015-11015 ◽  
Author(s):  
Jeanne Tie ◽  
Isaac Kinde ◽  
Hui-Li Wong ◽  
Joseph James McKendrick ◽  
Peter Gibbs ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Rank Test ◽  
Cancer Center ◽  
Circulating Dna ◽  
Plasma Samples ◽  
Mutational Status

11015 Background: Prognostic and predictive biomarkers in mCRC are urgently needed. Circulating tumor cells are a promising blood biomarker, but are detectable in only a minority of pts. Recently, analysis of circulating tumor DNA (ctDNA) has shown promise as a liquid biopsy, reflecting the evolving mutational status of the tumor. Here we explored baseline ctDNA as a prognostic marker, and early changes in ctDNA as a marker of CT response. Methods: Serial plasma samples and CEA were collected at baseline (D1), day 3 (D3) and cycle 2 day 1 (C2D1) from 40 mCRC pts receiving standard combination CT. Restaging scans performed at 8 weeks were centrally assessed using RECIST criteria. Samples were analyzed at Johns Hopkins Kimmel Cancer Center. Initially tumor tissue was analyzed for hotspot mutations in TP53, APC, KRAS, BRAF, PIK3CA and FBXW7. The same mutation was queried and quantified in plasma using a MPS platform (Safe-SeqS). Log-rank test was used to compare survival curves and Wilcoxon matched pairs test was used to compare paired plasma samples. Results: Preliminary data is available on 19 pts in this ongoing study. Using our initial panel at least 1 mutation was found in 16 of 19 (84.2%) tumors (7 KRAS, 3 TP53, 3 BRAF, 2 APC and 1 PIK3CA), with matching ctDNA found for each pt. For the remaining 3 cases a further panel of mutations is being analyzed. Median D1 cell free DNA (cfDNA) and ctDNA levels were 1.98 ng/ul (0.15 – 57.18) and 523 mutant fragments (frag)/ml (0.4 – 109,876), respectively. Pts with D1 cfDNA of ≥ 2.5 compared with < 2.5 had shorter median overall survival (OS; 6.9 v 12.2 months, p = 0.0086), with a trend for shorter progression-free survival (PFS; 3.6 v 8.2 months, p = 0.3477). A surge of ctDNA level from D1 to D3 was typically observed (median increase: 91.2 frag/ml, p = 0.0313), followed by a drop (median decrease from D1 to C2D1: 208.8 frag/ml, p = 0.0098). All pts with a decrease in ctDNA at C2D1 had a reduction in tumor size at 8 weeks. Conclusions: In all cases of mCRC where tumor mutation was identified, matching ctDNA was detected in plasma. Circulating DNA is a promising marker of prognosis. Early changes in DNA levels may be a useful marker of tumor response.

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

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