http:cancer'govedrn

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http//cancer.gov/edrn
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Early Detection Research NetworkBACKGROUND

• Proposed By
• Early Detection Implementation Group (Jan.-
  Aug., 1998)

• Approach Supported by
• Colon Cancer Progress Review Group (2001)
• Lung Cancer Progress Review Group (2002)
• Stomach and Esophageal Cancer Progress Review
  Group (2002)
• Pancreatic Cancer Progress Review Group (2002)
• Kidney and Bladder Cancer Progress Review Group
  (2002)
• Gynecologic Cancer Progress Review Group (2002)

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Early Detection Research Network GOALS

• Establish a National Infrastructure to support
  a vertical
• collaborative approach to move promising
  biomarker/technology to
• clinical validation
• Establish criteria for the validation
• Develop and institute quality assurance
  regimens
• Conduct early clinical and epidemiological
  studies to evaluate
• predictive value of biomarkers
• Promote Public- Private Partnership

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Goal Support Systematic Approach to Biomarker
Development

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Early Detection Research NetworkINVESTIGATOR-DRIV
EN CONSORTIUM
An infrastructure for supporting
collaborative research on molecular, genetic and
other biomarkers in human cancer detection and
risk assessment.
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EDRN LABORATORIES/CENTERS
Biomarkers Development Labs Johns Hopkins
University (2) University of Texas MD
Anderson University Maryland (2) University of
Colorado Yale University Northwestern University
Medical Center Moffitt Cancer Center, University
of South Florida University of Michigan University
of Texas Southwestern (2) Genetica, Inc. Duke
University Thomas Jefferson University University
of Pittsburgh Eastern Virginia Medical
School University of Washington, Seattle
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EDRN LABORATORIES/CENTERS
Clinical and Epidemiology Centers Johns Hopkins
University (2) University of Texas, MD
Anderson Brigham and Womens Hospital, Harvard
University Creighton University University of
Texas, San Antonio New York University University
of Michigan Center for Disease Control and
Prevention
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EDRN LABORATORIES/CENTERS
Biomarkers Validation Labs University of
California at Los Angeles University of Alabama
at Birmingham National Institute of Standards and
Technology
Data Management Fred Hutchinson Cancer Center

• Informatics
• Jet Propulsion Laboratory, California Institute
  of Technology,
• National Aeronautics and Space Administration

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EDRN Collaborative Groups
Collaborative Groups As a Gateway to Permeability

• Promote areas of research where collaboration
  will enhance technology, resource, and
  information sharing among EDRN and non-EDRN
  members
• Meet twice a year discuss collaborative matters
  twice a month through conference calls, emails,
  and listserv
• NCI and Collaborative Chairs conference calls
  every other month

1. Breast and Gynecologic Cancers 2. Colon and
Associated Gastrointestinal Cancers 3. Lung and
Upper Aerodigestive Cancers 4. Prostate and Other
Urologic Cancers
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EDRN Committees
Executive Committee
Meets monthly Approves collaborative studies,
validation studies, associate members,
supplements, other funding decisions
Steering Committee
Scientific management and oversight Monitors DMCC
activities Meets twice a year
Network Consulting Committee
Non-EDRN members Advise EDRN to meet its
goal Meets every two years
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Communicating with the Scientific Community

• EDRN Websites, Workshops, Working Group Meetings
• Gordon Research Conference on New Frontiers in
  Cancer Detection and Diagnosis, March 10-15,
  2002, Ventura, California
• Member Liaisons for relevant professional
  societies appointed
• Collaborative opportunities published in major
  journals
• Twenty Eight Associate Members approved

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Early Detection Research NetworkMILESTONES
April 2000 Early Detection Research Network
fully launched October 2000 Initial Report of
Early Detection Research Network published May
June 2001 Report presented to the NCA Board (May
26) and to the BSA (June 22) June 2001
Phases of Biomarkers Published October 2002
Second Progress Report Published November 2002
Progress Report presented to the BSA (Nov.
15) March 2003 First Clinical Validation
Study of Microsatellite Instability as a
Biomarker for Bladder Cancer

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PROGRESS TOWARD GOAL SUCCESSFUL INFRASTRUCTURE
That

• Represents a unique collaborative model based
  on
• division of labor
• Provides a collaborative platform for
  translational research
• Uses a flexible funding mechanism providing
  incentives for
• collaboration
• Empowers investigators for scientific
  leadership, research agenda
• and collaboration
• Employs continuous program evaluation
  benchmarks
• for measuring success

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PROGRESS TOWARD GOALS BUILDS ON MULTIPLE
RESOURCES

• Subjects exposed to environmental factors
• Multi-ethnic and multi-racial representation
• Hereditary cancers and high-risk cohorts for
• - Ovarian (Fishman and Cramer)
• - Prostate (Thompson and Partin)
• - Lung (Spitz and Rom)
• - Colon (Brenner, Lynch)
• - Pancreatic (Lynch)
• - Breast (Marks, Kiviat, Helzlsouer)
• Specimens with matching controls and
  epidemiological data

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PROGRESS TOWARD GOALSBUILDING INFORMATICS
Developed

• Common Data Elements, Statistical and
  Computational Tools, and
• other decision support tools
• EDRN Research Network Exchange ERNE to
  connect sites
• with biorepositories and other clinical
  databases (Virtual
• Warehouse)
• Web-based Portal for sharing data, exchanging
  data, and
• depositing data on specimens, protocols, IRB,
  etc.

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Early Detection Research Network Information
Exchange CLINICAL CENTERS CONNECTED
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PROGRESS TOWARD GOALSBUILDING MULTI PURPOSE
ANALYTICAL TOOLS

• Boosting Decision Trees
• Support Vector Machine
• Neural Network
• Binary Markers Combination Approach
• Biostatistical Classification Algorithm

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PROGESS TOWARD GOALS BIOMARKER DISCOVERY

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PROGRESS TOWARD GOALS BIOMARKER DISCOVERY
EXAMPLES
 

• EPIGENOMICS HYPERMETHYLATION
• Prostate GSTP1 (Sidransky)
• Lung (Gazdar,Tockman,Sidransky)
• GENOMIC EXPRESSION
• Barretts Esophagus (Meltzer)
• Breast BU101, BS 106 (Marks and Abbott Labs)
• Ovary Prostasin, Osteopontin (Cramer)
• PROTEIN PROFILING PATTERNS
• Breast (Trock, Wright, Liotta)
• Prostate (Wright)
• Ovarian (Liotta, Petricoin, Fishman)
• Lung Annexin 1 and 2, OP-18 (Hanash)

 
 
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PROGRESS TOWARD GOALS BIOMARKER DISCOVERY
TECHNOLOGY
 
cDNA array
Data Mining
SAGE

IN SILICO EXPRESSION
Gene Identification
Proteomics
PCR, Northern, Western
VALIDATION In situ, Primary Tumors, Blood
 
 
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PROGRESS TOWARD GOALS BIOMARKER FOR CANCER RISK
 
Organ
 
 
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• PROGRESS TOWARD GOALS
• PHASES OF DISCOVERY AND VALIDATION

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PROGRESS TOWARD GOALSVALIDATION STRATEGY
False Positive Rate False Negative Rate
More Stringent Threshold for Specificity and
Sensitivity
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Early Detection Research NetworkTIMELINE
VALIDATION STUDIES
Hyper- Methy
SELDIpr
Bladder MSI
MI-DNA
Oct 02
Apr 03
Oct 03
Apr 04
Oct 05
Apr 06

Phase I and II Validation
Phase III Validation
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PROGRESS TOWARD GOALS COLLABORATIONS

• Collaboration with NCIs Programs, SPORE, CGN,
  MMHCC
• Member Liaisons for Relevant Professional
  Societies Appointed, Including UICC and EORTC
• Collaboration with Several Federal Agencies
  NIST, JPL (NASA), CDCP and FDA
• 28 Associate Members Approved

.
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Core Funds

• Process For Collaboration
• (For Associate Membership)

EDRN PI sponsors AM using applic. for AM.
NCI Program forwards to Review Group
EDRN EC
Submits app. to NCI
RG recommends for approval to
NCI Grants Admin
NCI Program
EDRN EC recom- mends approval to NCI
NCI Program recom- mends for release to
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Core Funds
Validation Studies
NCI EDRN Program
EDRN Investigator
EDRN Executive Committee
If indicated to submit validation proposal...
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PROGRESS TOWARD GOALS COMMUNICATION AND
DISSEMINATION

• Public Wesbite (www.cancer.gov/edrn)
• Collaborative Opportunities thru Journals,
  Editorial
• Writings, Meetings and Conferences
• EDRN Biennial Progress Report
• Gordon Research Conference on Frontiers
• In Cancer Detection and Diagnosis in
  Collaboration
• With EDRN

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PROGRESS TOWARD GOALS
PUBLIC PRIVATE PARTNERSHIP
Bioinformatics/ Resources
EDRN
Basic Science
Academia
Industry
Clinical
Government
National Cancer Institute Centers for Disease
Control and Prevention National Institute of
Standards and Technology Jet Propulsion
Laboratory Food and Drug Administration
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PUBLIC-PRIVATE PARTNERSHIP

• Developed Successful Models for Industrial and
  Private
• Partnership
• Abbott and Vysis Diagnostics Ciphergen
• Merck Diagnostics Con Edison
• Organized Several EDRN Forums on Industrial
• Collaborations
• - EDRN Private-Public Partnership Workshop,
  September 5
• 2002. Ann Arbor, MI
• - EDRN-Human Proteome Organization Joint
  Workshop,
• September 5-6, 2002. Ann Arbor,
  MI

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Early Detection Research NetworkNEW OPPORTUNITIES

• Accelerate discovery and validation of
  technologies
• and newly discovered markers
• Expand Network to include additional organ sites
  and
• rare tumors (e.g., nasopharyngeal carcinoma,
• mesothelioma)
• Expand public-private partnership for validation
  studies
• by providing access to EDRN resources
• Develop comprehensive protein fingerprints for
• pre-malignant and pre-invasive cancers

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Early Detection Research NetworkSUMMARY AN
INVESTIGATOR-DRIVEN NETWORK
EDRN IS

• Interactive and driven by strong science
• Vibrant and collaborative
• Inclusive (Associate Members and outside
  collaborations)
• Dynamic with flexible funding structure
• Unique infrastructure with resources for
  translational research