cancer/edrn

1. http://cancer.gov/edrn

2. 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)

3. 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

4. Functional Genomics and Proteomics Fourth Generation Gene specific Mutations Third Generation Second Generation First Generation Serum Markers Gene Expression Profiles Goal: Support Systematic Approach to Biomarker Development

5. 18 Laboratories 3 Laboratories NIST 9 Centers CDCP Chair: Bernard Levin Chair: David Sidransky Early Detection Research NetworkINVESTIGATOR-DRIVEN CONSORTIUM An “infrastructure” for supporting collaborative research on molecular, genetic and other biomarkers in human cancer detection and risk assessment.

6. 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

7. EDRN LABORATORIES/CENTERS Clinical and Epidemiology Centers Johns Hopkins University (2) University of Texas, MD Anderson Brigham and Women’s Hospital, Harvard University Creighton University University of Texas, San Antonio New York University University of Michigan Center for Disease Control and Prevention

8. 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

9. 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

10. 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

11. 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 • Thirty-six Associate Members approved

12. 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

13. 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

14. PROGRESS TOWARD GOALS BUILDS ON MULTIPLERESOURCES • 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

15. 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.

16. Early Detection Research Network Information Exchange CLINICAL CENTERS CONNECTED

17. PROGRESS TOWARD GOALSBUILDING MULTI PURPOSE ANALYTICAL TOOLS • Boosting Decision Trees • Support Vector Machine • Neural Network • Binary Markers Combination Approach • Biostatistical Classification Algorithm

18. PROGESS TOWARD GOALS BIOMARKER DISCOVERY

19. PROGRESS TOWARD GOALS BIOMARKER DISCOVERY: EXAMPLES • EPIGENOMICS: HYPERMETHYLATION • Prostate: GSTP1 (Sidransky) • Lung (Gazdar,Tockman,Sidransky) • GENOMIC EXPRESSION: • Barrett’s 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)

20. 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

21. Marker Analysis Sample P I Prostate Protein Profiling of BPH, HPIN Machine Learning, AI,Wavelet Analysis Seminal Plasma, Serum Wright, Trock Lung Chromosomal Breakage, XPD Genotypes Case-Control Lymphocyte Spitz Prostate IGFb3/b4, AR Polymorphism Case-Control Lymphocyte Thompson Colon/HNPCC Pancreatic Cancer Mutations in Genes, MSI Hereditary high-risk cohorts Serum Lynch PROGRESS TOWARD GOALS BIOMARKER FOR CANCER RISK Organ

22. PROGRESS TOWARD GOALS PHASES OF DISCOVERY AND VALIDATION

23. BVLs Industry BDLs Biomarker Discovery Samples Lab : BDLs Clinical: CECs (Protocol Driven) Characterization (Phases 1 & 2) Cross-sectional Study Lab: BVL (High throughout CLIA Q/A, Q/C) Clinical: CEC Longitudinal Study Statistically Derived Panels of Biomarkers PROGRESS TOWARD GOALSVALIDATION STRATEGY False Positive Rate False Negative Rate More Stringent Threshold for Specificity and Sensitivity

24. 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

25. PROGRESS TOWARD GOALS COLLABORATIONS • Collaboration with NCI’s 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 • 36 Associate Members Approved .

26. 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 Program NCI Grants Admin EDRN EC recom- mends approval to NCI NCI Program recom- mends for release to

27. Core Funds Step 1 Submit pre-proposal or LOI to EC Step 2 EC Review of Pre-proposal or LOI • Review Decision: • Submit validation • proposal OR • Continue marker • development Success Step 3 Establish collaboration with CEC, DMCC, BVL, including NIST • Review Decision: • Fund study OR • Need more data • OR • Continue • development Need More Data Step 5 NCI forwards to EC. Review by EC or EDRN Review Group Step 4 Develop biomarker validation proposal; submit to NCI • Gather more data • Resubmit to EC • Appeal to EC Shelved Validation Studies EDRN Investigator NCI EDRN Program EDRN Executive Committee If indicated to submit validation proposal...

28. 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

29. 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

30. PUBLIC-PRIVATE PARTNERSHIP • DevelopedSuccessful Models for Industrial and Private • Partnership • Abbott and Vysis Diagnostics Ciphergen • Merck Diagnostics Con Edison • OrganizedSeveral 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

31. 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

32. 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