# Presentation: 308215

## http://cancer.gov/edrn

## Early Detection Research NetworkBACKGROUND

-    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)**

##  Early Detection Research Network GOALS

**   ****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**
**  **

** ****Early Detection Research Network ****GOALS**

## Goal: Support Systematic Approach to Biomarker Development

**  **

**Goal: Support Systematic Approach to Biomarker Development**

## Early Detection Research NetworkINVESTIGATOR-DRIVEN CONSORTIUM

***An “infrastructure”    for supporting collaborative research on molecular, genetic and other biomarkers in human cancer detection and risk assessment.***

**Early Detection Research Network****INVESTIGATOR-DRIVEN CONSORTIUM**

## EDRN LABORATORIES/CENTERS

**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**

**EDRN LABORATORIES/CENTERS**

## EDRN LABORATORIES/CENTERS

**Clinical and Epidemiology Centers**
**J****ohns 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**

**EDRN LABORATORIES/CENTERS**

## EDRN LABORATORIES/CENTERS

**Fred Hutchinson Cancer Center**

**Biomarkers Validation Labs**
**University of California at Los Angeles**
**University of Alabama at Birmingham**
**National Institute of Standards and Technology**

**EDRN LABORATORIES/CENTERS**

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

## EDRN Collaborative Groups

- 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

**Collaborative Groups As a Gateway**
** ****to Permeability**

**1. Breast and Gynecologic Cancers**
**2. Colon and Associated Gastrointestinal Cancers**
**3. Lung and Upper Aerodigestive Cancers**
**4. Prostate and Other Urologic Cancers**

## 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**

## Communicating with the Scientific Community

**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**

## Early Detection Research NetworkMILESTONES

_**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**
**                                   **

**Early Detection Research Network****MILESTONES**

## SUCCESSFUL INFRASTRUCTURE

** **

**PROGRESS TOWARD GOAL**
**SUCCESSFUL INFRASTRUCTURE**

**    ****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**

**That:**

##  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 **

** ****PROGRESS TOWARD GOALS**
-  **BUILDS ON MULTIPLE** **RESOURCES**

## PROGRESS TOWARD GOALSBUILDING INFORMATICS

**   ****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.**

**PROGRESS TOWARD GOALS****BUILDING INFORMATICS**

**Developed:**

**Early Detection Research Network Information Exchange**
**CLINICAL CENTERS CONNECTED**

## PROGRESS TOWARD GOALSBUILDING MULTI PURPOSE ANALYTICAL TOOLS

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

**PROGRESS TOWARD GOALS****BUILDING MULTI PURPOSE ANALYTICAL TOOLS**

## BIOMARKER DISCOVERY

| Target | Biomarker |
| --- | --- |
| Genomics | DNA (genes), e.g., mitochondrial DNA, expression analysis |
| Transcriptomics | mRNA |
| Proteomics | Proteins and their interactions |
| Metabolomics | Biochemical metabolites, e.g,
LPA, PSA, CEA-125,secreted proteins |
| Epigenomics | Hypermethylation, Acetylation, etc |

**PROGESS TOWARD GOALS**
**BIOMARKER DISCOVERY**

**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)**

**VALIDATION**
- In situ, Primary Tumors, Blood

**cDNA**
**array**

**Data Mining**

**SAGE**

**PCR, Northern, Western**

**Gene **
**Identification**

**Proteomics**

**IN SILICO**
**EXPRESSION**

**PROGRESS TOWARD GOALS**
**BIOMARKER DISCOVERY: TECHNOLOGY**

**Organ**

**PROGRESS TOWARD GOALS**
**BIOMARKER FOR CANCER RISK **

## PROGRESS TOWARD GOALS
PHASES OF DISCOVERY AND VALIDATION

**PROGRESS TOWARD GOALS**
**PHASES OF DISCOVERY AND VALIDATION**

**PROGRESS TOWARD GOALS****VALIDATION STRATEGY**

**False Positive Rate**
**False Negative Rate**

**More Stringent Threshold for  Specificity and Sensitivity **

##  Early Detection Research NetworkTIMELINE VALIDATION STUDIES

- Oct 02

- Apr 03

- Oct 03

- Apr 04

- Oct 05

- Apr 06

- Hyper-
- Methy

- SELDIpr

- Bladder
- MSI

- MI-DNA

**Phase I and II Validation**** **

** **

**Phase III Validation**

## COLLABORATIONS

**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**
**28 Associate Members Approved**

- .

## Core Funds

- Process For Collaboration
- (For Associate Membership)

- Submits app.
- to NCI

- EDRN PI
- sponsors AM
- using applic.
- for AM.

- RG recommends
- for approval to

- NCI Program
- forwards
- to Review
- Group

- EDRN EC

- NCI Program recom-
- mends for release to

- NCI
- Grants
- Admin

- EDRN EC recom-
- mends approval to NCI

- NCI
- Program

## Core Funds

- If indicated to submit
- validation proposal...

**EDRN Executive Committee**

**NCI EDRN Program**

**EDRN Investigator**

- Validation Studies

## COMMUNICATION AND DISSEMINATION 

-   **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**
**  **
** **

**PROGRESS TOWARD GOALS**
**COMMUNICATION AND DISSEMINATION**** **

## PUBLIC PRIVATE PARTNERSHIP

**Centers for Disease Control and Prevention**
**National Institute of Standards and Technology**
**Jet Propulsion Laboratory**
**Food and Drug Administration**

**Basic **
**Science**

**Bioinformatics/**
**Resources**

**Clinical**

**Industry**

**Academia**

**Government**

**EDRN**

** ****PROGRESS TOWARD GOALS**

**PUBLIC PRIVATE PARTNERSHIP**

## PUBLIC-PRIVATE PARTNERSHIP

**   ****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**
**  **
** **

**PUBLIC-PRIVATE PARTNERSHIP**

**Early Detection Research Network****NEW 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**

## Early Detection Research NetworkSUMMARY: 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**