Alliance of Glycobiologists for Detection of Cancer and Cancer Risk

1. Alliance of Glycobiologists for Detection of Cancer and Cancer Risk Karl Krueger, Ph.D. Division of Cancer Prevention

2. Web Cast Links • URL: http://videocast.nih.gov • Presentation slides: http://www.cancer.gov/edrn • To submit questions live use the Live Event Feedback Formhyperlink on the videocast site for this presentation.

3. Agenda • Elaboration on the RFA and the structure of the Alliance, 30 min: Karl Krueger, Ph.D. • The Early Detection Research Network, 15 min: • Sudhir Srivastava, Ph.D. MPH • The Consortium for Functional Glycomics, 15 min: • Pamela Marino, Ph.D. • Glycomics and Glycotechnology Resource Centers, 15 min: Douglas Sheeley, Sc.D. • Application submission and peer review, 15 min: • Marvin Salin, Ph.D.

4. Alliance’s Scientific Goals • Exploit the vast repertoire of glycan structures synthesized by tumor cells to identify novel biomarkers of cancer for early detection, diagnosis, recurrence, or cancer risk. • Promote clinical validation of glycan cancer biomarkers in case/control studies. • For glycan biomarkers exhibiting good performance (in terms of sensitivity and specificity), assist in developing tests that can be carried out in a clinical setting. • Note the translational emphasis of this initiative.

5. Guiding Principles for Biomarker Research: Phases of Early Detection Research

6. Early detection of cancer improvespatient survival and quality of life. Etzioni et al., Nature Reviews Cancer 3, 243-252 (2003)

7. Structure of the Alliance NCI Tumor Glycome Laboratories NIGMS – CFG NCRR – Glyco Centers Resources for carbohydrateanalysis and specializedglycomic reagents. NCI – EDRN Support for validation studies. Limited assistance with specimen access andindependent verificationof test results. Coordination Unit

8. Components of the Alliance • Tumor Glycome Laboratories – discover, develop, and present glycan biomarkers to EDRN for clinical validation; open competition for U01 funds • CFG & Glycomic Resource Centers – provide resources, expertise, reagents, assays and tools to facilitate tumor glycomic research • EDRN – provide the infrastructure for clinical validation of glycan biomarkers • Coordination Unit – provide oversight and offer direction for achieving the Alliance’s objectives (comprised of TGL PIs, CFG & EDRN chairs, and NCI, NIGMS, NCRR program staff)

9. Tumor Glycome Laboratories:Key Components Biomarker Discovery Component – led by PI of the U01; leads biomarker discovery/development effort Carbohydrate Analytical Component – if the PI lacks certain expertise in glycotechnology, collaboration with such experts is necessary Clinical Specimen Component – provides access for clinical specimens for testing biomarker performance Statistical Support Component – assists with study design and analysis of data

10. Tumor Glycome Laboratories:PI Requirements • Full participation as a voting member of the Coordination Unit (CU). Attendance at annual CU meetings and regular CU conference calls. • Data and Resource Sharing – facilitate research progress of the Alliance. Inform other Alliance members of current progress. Glycome profiles and novel glycan structures are to be deposited into the CFG databases. • Attendance annually at a relevant glycobiology- or biomarker-related meeting per year.

11. What is a U01? • PIs in the Alliance will be funded by the U01 Cooperative Agreement mechanism. This mechanism involves substantial programmatic involvement. • Although the level of funding will be similar to R01 grants, these will not be “isolated” research projects. The Alliance is designed to function as a team where the collaborative interactions of everyone facilitate the progress made by each laboratory, and by the consortium as a whole. • By partnering with the CFG and Glycotechnology Resource Centers, the Alliance has access to the most robust collection of resources and expertise for carbohydrate analysis. By partnering with EDRN, the Alliance gains the experience of leading laboratories that are successfully overcoming the obstacles encountered with biomarker development.

12. The Coordination Unit:Composition • Comprised of (voting members): i) Tumor Glycome Lab PIs ii) Chairs / Co-chairs or designees from EDRN and CFG iii) Program Staff from NCI, NIGMS, and NCRR • Chair of the CU will be a PI and voted on from among the members of the CU.

13. The Coordination Unit:Roles • The CU provides oversight and management of activities within the Alliance. Keeps current on developments within the Alliance and provides guidance to efficiently achieve the objective of clinical validation for glycan biomarkers. • At the outset, the CU will establish the “Rules of Engagement” for governing the operation of the Alliance. This will include considerations for policies and procedures for expenditure of Collaborative Resource Funds, modifying aims of existing research projects, or inviting the participation of other investigators with biomarkers that fit the goals of the Alliance.

14. Specific Application Details • PHS Form 398 • Sections A-D replaced by Sections 1-3 (35 page limit)Section 1 – Tumor Glycome Laboratory Team Section 2 – Scope of Research (like sections A-D) Section 3 – Collaborative Activities (prior/ongoing collaborations, data and resource sharing plans) • Direct Costs limited to $300,000Budget for 2 meetings per year (annual CU meeting and a glycobiology or biomarker-related meeting)

15. Imperatives • Be sure to address the priorities of this initiative. • Focus on cancer early detection, diagnosis, recurrence, or risk. (Specific aims must not propose therapeutic strategies, technology development, or basic cancer biology research.) • Goals must have translational impact. • Willingness to collaborate.

16. Key Dates Open Season for RFI: Dec. 2, 2005 – Mar. 1, 2006 RFA Release Date: June 15 Letter of Intent Receipt Date: July 23 (only 9 days left!!!) Application Receipt Date: August 23 Peer Review Dates: November 8-9 (tentative) Council Review: February 2007 Earliest Start Date: March 1, 2007