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Grant Details

Grant Number: 5U01CA182940-05 Interpret this number
Primary Investigator: Luebeck, Georg
Organization: Fred Hutchinson Cancer Research Center
Project Title: Esophageal Cancer From Cells to Population: a Multiscale Approach
Fiscal Year: 2017
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Abstract

DESCRIPTION (provided by applicant): Esophageal Cancer from Cells to Population: A Multiscale Approach The goal of the proposed research is to reduce the burden of esophageal adenocarcinoma (EAC) by optimizing surveillance of patients with Barrett's esophagus (BE) using cutting-edge endoscopic imaging and advanced epigenetic profiling of neoplastic tissues in combination with standard endoscopic techniques. To accomplish this goal we will establish a multidisciplinary collaboration between cancer biologists, epidemiologists, clinicians and computational and mathematical modelers. This research team will develop a multiscale modeling framework that synthesizes and integrates data generated from diverse sources and at different scales to provide a coherent and informative portrayal of the natural history of EAC. Simulation models of EAC actively supported by the NCI's CISNET (U01 CA152926) and data from the Barrett's Esophagus Translational Research Network (BETRNet, U54 CA163060) will serve as the foundation for a new biologically-motivated Multiscale Esophageal Adenocarcinoma Model (MEMo). This new model will be informed by data that span numerous scales including: molecular level DNA methylation data, cellular level volumetric laser endomicroscopy (VLE) data, patient level endoscopic surveillance data, and population level cancer registry SEER data. We will use MEMo as an analytic tool to assess the clinical effectiveness of BE surveillance protocols for early esophageal neoplasia detection and prevention. By the end of the award period, we will have an improved and more comprehensive understanding of the biological and natural history of EAC that provides a platform to design better strategies to control its population burden.

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Publications

Implications of epigenetic drift in colorectal neoplasia.
Authors: Luebeck G.E. , Hazelton W.D. , Curtius K. , Maden S.K. , Yu M. , Carter K.T. , Burke W. , Lampe P.D. , Li C.I. , Ulrich C.M. , et al. .
Source: Cancer Research, 2018-10-05 00:00:00.0; , .
EPub date: 2018-10-05 00:00:00.0.
PMID: 30291105
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Volumetric laser endomicroscopy interpretation and feature analysis in dysplastic Barrett's esophagus.
Authors: Kamboj A.K. , Kahn A. , Wolfsen H.C. , Trindade A.J. , Ganguly E.K. , Otaki F. , Chan D. , Zakko L. , Visrodia K. , Lutzke L. , et al. .
Source: Journal Of Gastroenterology And Hepatology, 2018 Oct; 33(10), p. 1761-1765.
EPub date: 2018-05-07 00:00:00.0.
PMID: 29633412
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Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis.
Authors: Yu M. , Maden S.K. , Stachler M. , Kaz A.M. , Ayers J. , Guo Y. , Carter K.T. , Willbanks A. , Heinzerling T.J. , O'Leary R.M. , et al. .
Source: Gut, 2018-06-08 00:00:00.0; , .
EPub date: 2018-06-08 00:00:00.0.
PMID: 29884612
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Editorial: The Effect of Bias on Estimation of Improved Survival After Diagnosis of Barrett's Esophagus.
Authors: Zakko L. , Visrodia K. , Wang K.K. , Iyer P.G. .
Source: The American Journal Of Gastroenterology, 2017 Aug; 112(8), p. 1265-1266.
PMID: 28766563
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Screening and Preventive Strategies in Esophagogastric Cancer.
Authors: Zakko L. , Lutzke L. , Wang K.K. .
Source: Surgical Oncology Clinics Of North America, 2017 Apr; 26(2), p. 163-178.
PMID: 28279462
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Cost-Effectiveness of Screening Patients with Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device.
Authors: Heberle C.R. , Omidvari A.H. , Ali A. , Kroep S. , Kong C.Y. , Inadomi J.M. , Rubenstein J.H. , Tramontano A.C. , Dowling E.C. , Hazelton W.D. , et al. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2017-02-23 00:00:00.0; , .
EPub date: 2017-02-23 00:00:00.0.
PMID: 28238953
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Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma.
Authors: Luebeck E.G. , Curtius K. , Hazelton W.D. , Maden S. , Yu M. , Thota P.N. , Patil D.T. , Chak A. , Willis J.E. , Grady W.M. .
Source: Clinical Epigenetics, 2017; 9, p. 113.
EPub date: 2017-10-16 00:00:00.0.
PMID: 29046735
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Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success.
Authors: Yankeelov T.E. , An G. , Saut O. , Luebeck E.G. , Popel A.S. , Ribba B. , Vicini P. , Zhou X. , Weis J.A. , Ye K. , et al. .
Source: Annals Of Biomedical Engineering, 2016 Sep; 44(9), p. 2626-41.
PMID: 27384942
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MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus.
Authors: Bansal A. , Gupta V. , Wang K. .
Source: Journal Of Cellular Biochemistry, 2016 Jun; 117(6), p. 1288-95.
PMID: 26808728
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Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett's esophagus.
Authors: Leggett C.L. , Gorospe E.C. , Chan D.K. , Muppa P. , Owens V. , Smyrk T.C. , Anderson M. , Lutzke L.S. , Tearney G. , Wang K.K. .
Source: Gastrointestinal Endoscopy, 2016 May; 83(5), p. 880-888.e2.
PMID: 26344884
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Diagnosing gastrointestinal illnesses using fecal headspace volatile organic compounds.
Authors: Chan D.K. , Leggett C.L. , Wang K.K. .
Source: World Journal Of Gastroenterology, 2016-01-28 00:00:00.0; 22(4), p. 1639-49.
PMID: 26819529
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Global Dna Methylation Patterns In Barrett's Esophagus, Dysplastic Barrett's, And Esophageal Adenocarcinoma Are Associated With Bmi, Gender, And Tobacco Use
Authors: Kaz A.M. , Wong C.J. , Varadan V. , Willis J.E. , Chak A. , Grady W.M. .
Source: Clinical Epigenetics, 2016; 8, p. 111.
PMID: 27795744
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Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus.
Authors: Yu M. , O'Leary R.M. , Kaz A.M. , Morris S.M. , Carter K.T. , Chak A. , Chandar A. , Willis J.E. , Moinova H.R. , Markowitz S.D. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Dec; 24(12), p. 1890-7.
PMID: 26545406
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The Role of Gastroesophageal Reflux and Other Factors during Progression to Esophageal Adenocarcinoma.
Authors: Hazelton W.D. , Curtius K. , Inadomi J.M. , Vaughan T.L. , Meza R. , Rubenstein J.H. , Hur C. , Luebeck E.G. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Jul; 24(7), p. 1012-23.
PMID: 25931440
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Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma.
Authors: Kaz A.M. , Grady W.M. , Stachler M.D. , Bass A.J. .
Source: Gastroenterology Clinics Of North America, 2015 Jun; 44(2), p. 473-89.
PMID: 26021206
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A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.
Authors: Curtius K. , Hazelton W.D. , Jeon J. , Luebeck E.G. .
Source: Plos Computational Biology, 2015 May; 11(5), p. e1004272.
PMID: 26001209
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Cost considerations in implementing a screening and surveillance strategy for Barrett's oesophagus.
Authors: Inadomi J.M. .
Source: Best Practice & Research. Clinical Gastroenterology, 2015 Feb; 29(1), p. 51-63.
PMID: 25743456
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MethyLight droplet digital PCR for detection and absolute quantification of infrequently methylated alleles.
Authors: Yu M. , Carter K.T. , Makar K.W. , Vickers K. , Ulrich C.M. , Schoen R.E. , Brenner D. , Markowitz S.D. , Grady W.M. .
Source: Epigenetics, 2015; 10(9), p. 803-9.
PMID: 26186366
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Prediction of response to endoscopic therapy of Barrett's dysplasia by using genetic biomarkers.
Authors: Timmer M.R. , Brankley S.M. , Gorospe E.C. , Sun G. , Lutzke L.S. , Iyer P.G. , Halling K.C. , Krishnadath K.K. , Wang K.K. .
Source: Gastrointestinal Endoscopy, 2014 Dec; 80(6), p. 984-91.
PMID: 25085335
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Barrett's Esophagus Translational Research Network (BETRNet): the pivotal role of multi-institutional collaboration in esophageal adenocarcinoma research.
Authors: Abrams J.A. , Appelman H.D. , Beer D.G. , Berry L.D. , Chak A. , Falk G.W. , Fitzgerald R.C. , Ginsberg G.G. , Grady W.M. , Joshi B.P. , et al. .
Source: Gastroenterology, 2014 Jun; 146(7), p. 1586-90.
PMID: 24768332
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Volumetric laser endomicroscopy detects subsquamous Barrett's adenocarcinoma.
Authors: Leggett C.L. , Gorospe E. , Owens V.L. , Anderson M. , Lutzke L. , Wang K.K. .
Source: The American Journal Of Gastroenterology, 2014 Feb; 109(2), p. 298-9.
PMID: 24496431
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Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm.
Authors: Sun X. , Elston R.C. , Barnholtz-Sloan J.S. , Falk G.W. , Grady W.M. , Faulx A. , Mittal S.K. , Canto M. , Shaheen N.J. , Wang J.S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 05; 25(5), p. 727-35.
PMID: 26929243
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A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett's Esophagus.
Authors: Curtius K. , Wong C.J. , Hazelton W.D. , Kaz A.M. , Chak A. , Willis J.E. , Grady W.M. , Luebeck E.G. .
Source: Plos Computational Biology, 2016 05; 12(5), p. e1004919.
PMID: 27168458
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Breath Testing for Barrett's Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device.
Authors: Chan D.K. , Zakko L. , Visrodia K.H. , Leggett C.L. , Lutzke L.S. , Clemens M.A. , Allen J.D. , Anderson M.A. , Wang K.K. .
Source: Gastroenterology, 2017 01; 152(1), p. 24-26.
EPub date: 2016-11-05 00:00:00.0.
PMID: 27825962
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