Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by Detecting Circulating Tumor DNA in Urine
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 +12 more
TLDR
The modeling of tumor lysis through the day-to-day kinetics of ctDNA released into the blood and then into the urine is demonstrated in this proof-of-concept study in lung cancer patients receiving anti-EGFR tyrosine kinase inhibitors, suggesting drug-induced tumor apoptosis within days of initial dosing.Abstract:
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. Results: Eight of nine evaluable NSCLC patients had detectable T790M-mutant DNA fragments in pre-treatment baseline samples. Daily monitoring of mutations in urine indicated a pattern of intermittent spikes throughout week 1 suggesting apoptosis with an overall decrease in fragment numbers between baselines to day 7 preceding radiographic response assessed at 6-12 weeks. Conclusions: These findings suggest drug-induced tumor apoptosis within days of initial dosing. Daily sampling of ctDNA may enable early assessment of patient response and proof-of-concept studies for drug development.read more
Citations
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Application of Cell-free DNA Analysis to Cancer Treatment
TL;DR: The capacity to detect new cancers, treatment-resistant variants, and tumor heterogeneity by noninvasive technology on the basis of tumor DNA in oncology by non invasive technology is demonstrated.
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Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC
Christian Rolfo,Philip C. Mack,Giorgio V. Scagliotti,Paul Baas,Fabrice Barlesi,Trever G. Bivona,Roy S. Herbst,Tony Mok,Nir Peled,Robert Pirker,Luis E. Raez,Martin Reck,Jonathan W. Riess,Lecia V. Sequist,Frances A. Shepherd,Lynette M. Sholl,Daniel Shao-Weng Tan,Heather A. Wakelee,Ignacio I. Wistuba,Murry W. Wynes,David P. Carbone,Fred R. Hirsch,David R. Gandara +22 more
TL;DR: It is concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.
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The emerging role of cell-free DNA as a molecular marker for cancer management.
TL;DR: Recent advancements are explored and the current gaps in knowledge concerning each point of contact between cfDNA analysis and the different stages of cancer management are highlighted.
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A field guide for cancer diagnostics using cell-free DNA: From principles to practice and clinical applications.
Anna-Lena Volckmar,Holger Sültmann,Anja Lisa Riediger,Thoas Fioretos,Peter Schirmacher,Volker Endris,Albrecht Stenzinger,Albrecht Stenzinger,Steffen Dietz +8 more
TL;DR: A variety of pre‐analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR‐based single locus assays to genome‐wide approaches are available, which considerably differ in sensitivity, specificity, and throughput.
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Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments
Saife Niaz Lone,Sabah Nisar,Tariq Masoodi,Mayank Singh,Arshi Rizwan,Sheema Hashem,Wael El-Rifai,Davide Bedognetti,Surinder K. Batra,Mohammad Haris,Ajaz A. Bhat,Muzafar A. Macha +11 more
TL;DR: A review of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes can be found in this article .
References
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Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies
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TL;DR: The ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types was evaluated and suggested that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes.
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Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
Tony Mok,Yi-Long Wu,Myung-Ju Ahn,Marina Chiara Garassino,Hye Ryoun Kim,Suresh S. Ramalingam,Frances A. Shepherd,Yong He,Hiroaki Akamatsu,Willemijn S. M. E. Theelen,Chee Khoon Lee,Martin Sebastian,A. Templeton,Helen Mann,Marcelo Marotti,Serban Ghiorghiu,Vassiliki A. Papadimitrakopoulou +16 more
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Journal Article
DNA Fragments in the Blood Plasma of Cancer Patients: Quantitations and Evidence for Their Origin from Apoptotic and Necrotic Cells
Sabine Jahr,Hannes Hentze,Sabine Englisch,Dieter Hardt,Frank O. Fackelmayer,Rolf-Dieter Hesch,Rolf Knippers +6 more
TL;DR: By quantitative methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor gene, the fraction of plasma DNA derived from tumor cells is quantified and is consistent with the possibility that apoptotic and necrotic cells are a major source for plasma DNA in cancer patients.
Journal ArticleDOI
Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
Sarah-Jane Dawson,Dana W.Y. Tsui,Muhammed Murtaza,Heather Biggs,Oscar M. Rueda,Suet-Feung Chin,Mark J Dunning,Davina Gale,Tim Forshew,Betania Mahler-Araujo,Sabrina Rajan,Sean Humphray,Jennifer Becq,David Halsall,Matthew G. Wallis,David Bentley,Carlos Caldas,Nitzan Rosenfeld +17 more
TL;DR: This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer.
Journal ArticleDOI
Liquid Biopsies: Genotyping Circulating Tumor DNA
Luis A. Diaz,Alberto Bardelli +1 more
TL;DR: The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.
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