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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/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
#2
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/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
#3
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/28428148/plasma-ctdna-analysis-for-detection-of-the-egfr-t790m-mutation-in-patients-with-advanced-non-small-cell-lung-cancer
#4
Suzanne Jenkins, James C-H Yang, Suresh S Ramalingam, Karen Yu, Sabina Patel, Susie Weston, Rachel Hodge, Mireille Cantarini, Pasi A Jänne, Tetsuya Mitsudomi, Glenwood D Goss
INTRODUCTION: Tumor biopsies for detecting epidermal growth factor receptor mutations (EGFRm) in advanced non-small cell lung cancer (NSCLC) are invasive, costly and not always feasible for patients with late-stage disease. The clinical utility of the cobas(®) EGFR Mutation Test v2 with plasma samples from patients with NSCLC at disease progression following previous EGFR-tyrosine kinase inhibitor (TKI) therapy was investigated to determine osimertinib treatment eligibility. METHODS: Matched tumor tissue and plasma samples from patients screened for AURA extension and AURA2 phase II studies were tested for EGFRm using tissue- and plasma-based cobas(®) EGFR Mutation Tests v2...
April 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28424201/pik3ca-mutations-contribute-to-acquired-cetuximab-resistance-in-metastatic-colorectal-cancer-patients
#5
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/28420725/monitoring-daily-dynamics-of-early-tumor-response-to-targeted-therapy-by-detecting-circulating-tumor-dna-in-urine
#6
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
#7
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/28419195/plasma-ctdna-ras-mutation-analysis-for-the-diagnosis-and-treatment-monitoring-of-metastatic-colorectal-cancer-patients
#8
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/28415658/diagnostic-and-prognostic-value-of-blood-samples-for-kras-mutation-identification-in-lung-cancer-a-meta-analysis
#9
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/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#10
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/28396313/acquired-met-y1248h-and-d1246n-mutations-mediate-resistance-to-met-inhibitors-in-non-small-cell-lung-cancer
#11
An-Na Li, Jinji Yang, Xu-Chao Zhang, Zhou Zhang, Jian Su, Lan-Ying Gou, Yu Bai, Qing Zhou, Zhenfan Yang, Han Han-Zhang, Wenzhao Zhong, Shannon Chuai, Qi Zhang, Zhi Xie, Hong-Fei Gao, Hua-Jun Chen, Zheng Wang, Zhen Wang, Xue-Ning Yang, Bin-Chao Wang, Bin Gan, Zhihong Chen, Ben-Yuan Jiang, Si-Pei Wu, Si-Yang Liu, Chongrui Xu, Yi-Long Wu
Purpose: MET amplification, responsible for 20% of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in patients with advanced non-small cell lung cancer (NSCLC), presents an attractive target. Numerous studies have conferred susceptibility of MET mutations and focal amplification to targeted MET-TKIs. However, the mechanism underlying MET-TKIs-induced resistance remains elusive. <p>Experimental Design: We conducted a cohort of 12 patients with advanced NSCLC who developed resistance to a combinatorial therapy consisting of gefitinib and a Type I MET-TKI...
April 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28392802/capturing-genomic-evolution-of-lung-cancers-through-liquid-biopsy-for-circulating-tumor-dna
#12
REVIEW
Michael Offin, Jacob J Chabon, Pedram Razavi, James M Isbell, Charles M Rudin, Maximilian Diehn, Bob T Li
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...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/28392479/circulating-tumor-dna-as-biomarkers-for-cancer-detection
#13
REVIEW
Xiao Han, Junyun Wang, Yingli Sun
Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ctDNA detection in various types of cancers has been attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early diagnosis and treatment of cancers...
April 6, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28385781/monitoring-of-multiple-myeloma-by-quantification-of-recurrent-mutations-in-serum
#14
Even Holth Rustad, Eivind Coward, Emilie R Skytøen, Kristine Misund, Toril Holien, Therese Standal, Magne Børset, Vidar Beisvag, Ola Myklebost, Leonardo A Meza-Zepeda, Hong Yan Dai, Anders Sundan, Anders Waage
Circulating tumor DNA (ctDNA) is a promising biomarker to monitor tumor load and genome alterations. We have explored the presence of ctDNA in multiple myeloma patients and its relation to disease activity during long-term follow-up. We used digital droplet PCR to monitor recurrent mutations, mainly in mitogen activated protein kinase pathway genes NRAS, KRAS and BRAF. Mutations were identified by next generation sequencing or PCR of bone marrow plasma cells, and their presence analyzed in 251 archived serum samples obtained from 20 patients during up to 7 years...
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28373672/circulating-tumor-dna-mutation-profiling-by-targeted-next-generation-sequencing-provides-guidance-for-personalized-treatments-in-multiple-cancer-types
#15
Yongqian Shu, Xue Wu, Xiaoling Tong, Xiaonan Wang, Zhili Chang, Yu Mao, Xiaofeng Chen, Jing Sun, Zhenxin Wang, Zhuan Hong, Liangjun Zhu, Chunrong Zhu, Jun Chen, Ying Liang, Huawu Shao, Yang W Shao
Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28368455/tracking-a-cad-alk-gene-rearrangement-in-urine-and-blood-of-a-colorectal-cancer-patient-treated-with-an-alk-inhibitor
#16
G Siravegna, A Sartore-Bianchi, B Mussolin, A Cassingena, A Amatu, L Novara, M Buscarino, G Corti, G Crisafulli, A Bartolini, F Tosi, M Erlander, F Di Nicolantonio, S Siena, A Bardelli
Background: Monitoring response and resistance to kinase inhibitors is essential to precision cancer medicine, and is usually investigated by molecular profiling of a tissue biopsy obtained at progression. However, tumor heterogeneity and tissue sampling bias limit the effectiveness of this strategy. In addition, tissue biopsies are not always feasible and are associated with risks due to the invasiveness of the procedure. To overcome these limitations, blood-based liquid biopsy analysis has proven effective to non-invasively follow tumor's clonal evolution...
March 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28368441/concordance-of-blood-and-tumor-based-detection-of-ras-mutations-to-guide-anti-egfr-therapy-in-metastatic-colorectal-cancer
#17
J Grasselli, E Elez, G Caratù, J Matito, C Santos, T Macarulla, J Vidal, M Garcia, J M Viéitez, D Paéz, E Falcó, C Lopez Lopez, E Aranda, F Jones, V Sikri, P Nuciforo, R Fasani, J Tabernero, C Montagut, D Azuara, R Dienstmann, R Salazar, A Vivancos
BACKGROUND: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-EGFR therapy. PATIENTS AND METHODS: A prospective-retrospective cohort study was performed. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue...
March 20, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28356236/characterization-of-the-groove-binding-between-di-2-ethylhexyl-phthalate-and-calf-thymus-dna
#18
Song Li, Junhui Pan, Guowen Zhang, Jianjian Xu, Deming Gong
In this study, the interaction between di-(2-ethylhexyl) phthalate (DEHP) and calf thymus DNA (ctDNA) was investigated by a combination of multispectroscopic methods, chemometrics algorithm, cyclic voltammetry and molecular simulation. The concentration profiles of the components obtained from resolving the UV-vis absorption data by multivariate curve resolution-alternating least-squares (MCR-ALS) provided a basic evidence for the formation of DEHP-ctDNA complex. Furthermore, the groove binding of DEHP to ctDNA was evidenced by the results from iodide quenching effect, single-stranded DNA quenching effect, melting studies, viscosity measurements and cyclic voltammetry...
March 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28341106/the-apple-trial-feasibility-and-activity-of-azd9291-osimertinib-treatment-on-positive-plasma-t790m-in-egfr-mutant-nsclc-patients-eortc-1613
#19
Jordi Remon, Jessica Menis, Baktiar Hasan, Aleksandra Peric, Eleonora De Maio, Silvia Novello, Martin Reck, Thierry Berghmans, Bartosz Wasag, Benjamin Besse, Rafal Dziadziuszko
The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28340710/selective-colorimetric-analysis-of-spermine-based-on-the-cross-linking-aggregation-of-gold-nanoparticles-chain-assembly
#20
Jian Wang, Zhu Lian Wu, Hong Zhi Zhang, Yuan Fang Li, Cheng Zhi Huang
A selective colorimetric assay for spermine was proposed in this work. In a weak alkaline medium, the conformational structure of double-stranded calf thymus DNA (ctDNA) was loosened to install gold nanoparticles (AuNPs) into chains. While, the chain assembly of AuNPs could form cross-linking aggregates when spermine was present, which was attributed to the electrostatic interaction between the positive change of spermine and negative change both of AuNPs and ctDNA, as well as the groove binding between ctDNA and spermine...
May 15, 2017: Talanta
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