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https://www.readbyqxmd.com/read/28431643/advances-in-circulating-tumor-dna-analysis
#1
Samantha Perakis, Martina Auer, Jelena Belic, Ellen Heitzer
The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool and might revolutionize cancer care with respect to early detection, identification of minimal residual disease, assessment of treatment response, and monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy" offers what tissue biopsies cannot-a continuous monitoring of tumor-specific changes during the entire course of the disease. Owing to technological improvements, efforts for the establishment of preanalytical and analytical benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual clinical implementation has come within easy reach...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28431544/strategies-for-monitoring-and-combating-resistance-to-combination-kinase-inhibitors-for-cancer-therapy
#2
REVIEW
Leanne G Ahronian, Ryan B Corcoran
Targeted therapies such as kinase inhibitors and monoclonal antibodies have dramatically altered cancer care in recent decades. Although these targeted therapies have improved patient outcomes in several cancer types, resistance ultimately develops to these agents. One potential strategy proposed to overcome acquired resistance involves taking repeat tumor biopsies at the time of disease progression, to identify the specific molecular mechanism driving resistance in an individual patient and to select a new agent or combination of agents capable of surmounting that specific resistance mechanism...
April 21, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28431395/correlation-of-genomic-alterations-assessed-by-next-generation-sequencing-ngs-of-tumor-tissue-dna-and-circulating-tumor-dna-ctdna-in-metastatic-renal-cell-carcinoma-mrcc-potential-clinical-implications
#3
Andrew W Hahn, David M Gill, Benjamin Maughan, Archana Agarwal, Lubina Arjyal, Sumati Gupta, Jessica Streeter, Erin Bailey, Sumanta K Pal, Neeraj Agarwal
INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430637/clinical-utility-of-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-gastric-cancer
#4
Katsutoshi Shoda, Daisuke Ichikawa, Yuji Fujita, Kiyoshi Masuda, Hidekazu Hiramoto, Junichi Hamada, Tomohiro Arita, Hirotaka Konishi, Toshiyuki Kosuga, Shuhei Komatsu, Atsushi Shiozaki, Kazuma Okamoto, Issei Imoto, Eigo Otsuji
Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430611/prognostic-value-of-egfr-and-kras-in-circulating-tumor-dna-in-patients-with-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#5
REVIEW
Gaowei Fan, Kuo Zhang, Jiansheng Ding, Jinming Li
EGFR (exon 19 and exon 21) mutations in patients with advanced non-small cell lung cancer (NSCLC) treated by EGFR-TKIs are associated with a better survival; while KRAS mutations predict a worse prognosis. However, there are divergent findings regarding the prognostic value of EGFR and KRAS mutations in circulating tumor DNA (ctDNA). We aimed to summarize the evidence for the use of circulating EGFR and KRAS mutations as prognostic factors in advanced NSCLC patients.We searched the network databases for studies reporting progression-free survival (PFS) and overall survival (OS) stratified by EGFR or KRAS mutations in ctDNA in advanced NSCLC patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424339/discovery-of-double-stranded-genomic-dna-in-circulating-exosomes
#6
Raghu Kalluri, Valerie S LeBleu
It is becoming increasingly clear that small vesicles released from cells (extracellular vesicles [EVs]) represent a heterogeneous population implicated in cell-to-cell communication. The classifications and nomenclature of EVs are evolving as enrichment strategies and specific characteristics are being unraveled. At present, physical properties of EVs-namely, size, shape, and density-are often used to identify subpopulations of EVs. A distinct group of EVs, termed exosomes, largely defined by their small size (∼40-150 nm) and proposed subcellular origin, has been extensively studied in several aspects of cancer biology...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28424201/pik3ca-mutations-contribute-to-acquired-cetuximab-resistance-in-metastatic-colorectal-cancer-patients
#7
Jian Ming Xu, Yan Wang, You-Liang Wang, Yan Wang, Tao Liu, Ming Ni, Man-Sheng Li, Li Lin, Fei-Jiao Ge, Chun Gong, Jun-Yan Gu, Ru Jia, He-Fei Wang, Yu Ling Chen, Rong-Rui Liu, Chuan-Hua Zhao, Zhao-Li Tan, Yang Jin, Yunping Zhu, Shuji Ogino, Zhi Rong Qian
<p>Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential roles of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.</p> <br /><br />Experimental Design: <p>Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#8
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420725/monitoring-daily-dynamics-of-early-tumor-response-to-targeted-therapy-by-detecting-circulating-tumor-dna-in-urine
#9
Hatim Husain, Vladislava O Melnikova, Karena Kosco, Brian Woodward, Soham More, Sandeep C Pingle, Elizabeth Weihe, Ben Ho Park, Muneesh Tewari, Mark G Erlander, Ezra E W Cohen, Scott M Lippman, Razelle Kurzrock
Purpose: Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design : We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420618/research-progress-on-liquid-biopsy-in-oncology-and-its-clinical-applications
#10
Wang Chen, Li Yanming, Fang Xiangdong
Liquid biopsy is an emerging and promising detection tool for cancer, with the benefit of being non-invasive and convenient. It analyzes tumor-derived information in the blood or other body fluids including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion of liquid biopsy research contents and the development of capture and detection technologies, liquid biopsy is increasingly utilized in clinical applications, promoting the development of tumor precision medicine...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28420468/-effect-of-heparin-pretreatment-on-the-level-of-neutrophil-extracellular-traps-of-serum-and-lung-tissue-in-septic-mice
#11
Jing Jiang, Shengtian Mu, Fangxiao Zhang, Yanting Qiao, Yongran Wu, Zhidan Zhang, Xiaochun Ma
OBJECTIVE: To investigate the influence of heparin pretreatment on serum and lung tissue level of neutrophil extracellular traps (NETs) in septic mice model and its molecular mechanism. METHODS: Ninety male C57BL/6J mice were randomly divided into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg LPS in 100 ?L normal saline was intraperitoneally injected) and LPS+heparin group (n = 30, 8 U of heparin in 20 ?L normal saline was subcutaneously injected 30 minutes before the injection of LPS)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28419195/plasma-ctdna-ras-mutation-analysis-for-the-diagnosis-and-treatment-monitoring-of-metastatic-colorectal-cancer-patients
#12
J Vidal, L Muinelo, A Dalmases, F Jones, D Edelstein, M Iglesias, M Orrillo, A Abalo, C Rodríguez, E Brozos, Y Vidal, S Candamio, F Vázquez, J Ruiz, M Guix, L Visa, V Sikri, J Albanell, B Bellosillo, R López, C Montagut
Background: RAS assessement is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28417079/detection-of-copy-number-alterations-in-cell-free-tumor-dna-from-plasma
#13
Olga Østrup, Lise Barlebo Ahlborn, Ulrik Lassen, Morten Mau-Sørensen, Finn Cilius Nielsen
BACKGROUND: Somatic copy number alterations (SCNAs) occurring in tumors can provide information about tumor classification, patient's outcome or treatment targets. Liquid biopsies, incl. plasma samples containing circulating cell-free tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however specify and reliability of methods have to be tested. METHODS: SNP microarrays (Affymetrix) were used to generate whole-genome copy number profiles from plasma ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with metastatic cancers...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28416949/circulating-tumor-dna-in-a-breast-cancer-patient-s-plasma-represents-driver-alterations-in-the-tumor-tissue
#14
Jieun Lee, Sung-Min Cho, Min Sung Kim, Sug Hyung Lee, Yeun-Jun Chung, Seung-Hyun Jung
Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416241/circulating-tumor-dna-from-bench-to-bedside
#15
Joline S J Lim, Filip Janku, Timothy A Yap
In the era of personalized medicine, tumor sampling is paramount to enable the assessment of actionable molecular aberrations to help rationalize and guide treatment decisions. Longitudinal tracking of such aberrations may also be helpful to detect emerging drug resistance and to allow for timely modifications to ongoing therapies to improve patient outcomes. Nevertheless, tumor tissue sampling involves an invasive procedure with potential risks to patients and involves logistical challenges. As such, other less invasive and safer methods such as blood sampling for molecular profiling has been gaining traction...
March 1, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28415895/the-value-of-liquid-biopsy-in-diagnosis-and-monitoring-of-diffuse-large-b-cell-lymphoma-recent-developments-and-future-potential
#16
Vincent Camus, Fabrice Jardin, Herve Tilly
Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous subset of non-Hodgkin lymphomas (NHL) that demonstrate many molecular alterations and somatic mutations, all of which are targets for the recent development of biomarkers that use various molecular biological techniques. These non-invasive emerging biomarkers will be used in the next few years to better monitor the response to immunochemotherapeutic treatments with the aim of completely eradicating the disease in order to cure it. Areas covered: In this review, the authors conducted a literature search to identify and summarize the major advances in liquid biopsy techniques for DLBCL that are useful for diagnosis and monitoring minimal residual disease (MRD)...
April 18, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28415658/diagnostic-and-prognostic-value-of-blood-samples-for-kras-mutation-identification-in-lung-cancer-a-meta-analysis
#17
REVIEW
Hongchang Shen, Keying Che, Lei Cong, Wei Dong, Tiehong Zhang, Qi Liu, Jiajun Du
Circulating tumor DNA (ctDNA) and tumor cells (CTC) are novel approaches for identifying genomic alterations. Thus, we designed a meta-analysis to evaluate the diagnostic value and prognostic significance of a KRAS proto-oncogene, GTPase (KRAS) mutation for lung cancer patients. All included articles were from PubMed, EMBASE, Web of Science and Cochrane Library. Twelve articles that described 1,131 patients were reviewed. True positives (TP), false positives (FP), true negatives (TN), and false negatives (FN) were used to calculate pooled sensitivity, specificity, the positive likelihood ratio (PLR), the negative likelihood ratio (NLR), a diagnostic odds ratio (DOR), the area under the curve (AUC) and corresponding 95% confidence intervals (95% CI)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414925/reversion-of-brca1-2-germline-mutations-detected-in-circulating-tumor-dna-from-patients-with-high-grade-serous-ovarian-cancer
#18
Elizabeth L Christie, Sian Fereday, Ken Doig, Swetansu Pattnaik, Sarah-Jane Dawson, David D L Bowtell
Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC. Patients and Methods Plasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation...
April 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#19
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28410618/liquid-biopsy-a-step-forward-towards-precision-medicine-in-urologic-malignancies
#20
REVIEW
Ashley Di Meo, Jenni Bartlett, Yufeng Cheng, Maria D Pasic, George M Yousef
There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers...
April 14, 2017: Molecular Cancer
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