AD_________________ Award Number: W81XWH-06-1-0749
TITLE: Harnessing Functional Genomics to Reverse Chemoresistance in Breast Cancer
PRINCIPAL INVESTIGATOR: Brian Bodemann
CONTRACTING ORGANIZATION: University of Texas Southwestern Medical Center at Dallas Dallas, TX 75390 REPORT DATE: October 2008
TYPE OF REPORT: Annual Summary
PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012
DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited
The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation.
Form Approved OMB No. 0704-0188
REPORT DOCUMENTATION PAGE
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1. REPORT DATE
2. REPORT TYPE
3. DATES COVERED
Annual Summary
1 Oct 2008
15 Sep 2007 – 14 Sep 2008
4. TITLE AND SUBTITLE
5a. CONTRACT NUMBER
Harnessing Functional Genomics to Reverse Chemoresistance in Breast Cancer
5b. GRANT NUMBER
W81XWH-06-1-0749 5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S)
5d. PROJECT NUMBER
Brian Bodemann
5e. TASK NUMBER
E-Mail:
[email protected]
5f. WORK UNIT NUMBER
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)
8. PERFORMING ORGANIZATION REPORT NUMBER
University of Texas Southwestern Medical Center at Dallas Dallas, TX 75390
9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)
10. SPONSOR/MONITOR’S ACRONYM(S)
U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012
11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT
Approved for Public Release; Distribution Unlimited
13. SUPPLEMENTARY NOTES
14. ABSTRACT
Targeted therapy has proven to be an effective strategy in the treatment of breast cancer. An example of successful targeted therapy is trastuzumab, a humanized monoclonal antibody binds to the extracellular domain of HER2, a receptor which is overexpressed in many breast cancers. The goal of my project is to identify molecular targets for conjunctive therapy that will increase efficacy of trastuzumab therapy. To identify molecular targets necessary for breast cancer cell survival in the presence of trastuzumab, a breast cancer cell line with known cytostatic sensitivity to trastuzumab, will be screened using a high throughput assay using a with a unique small interfering (si)RNA library targeting all 21,125 known genes in the human genome database. This information will help identify new synergistic combinations with existing drugs and novel therapeutic targets that can act synergistically as initial therapy and upon the development of resistance. During the time covered by this annual summary, I have uncovered an important signaling nexus regulating cell survival and drug resistance in breast cancer cells.
15. SUBJECT TERMS
Genomics, breast, cancer, siRNA, screen, Herceptin, trastuzumab
16. SECURITY CLASSIFICATION OF: a. REPORT
U
b. ABSTRACT
U
17. LIMITATION OF ABSTRACT
18. NUMBER OF PAGES
c. THIS PAGE
U
19a. NAME OF RESPONSIBLE PERSON
USAMRMC
19b. TELEPHONE NUMBER (include area
UU
20
code)
Table of Contents Page
Introduction
4
Body
5-9
Key Training Accomplishments
10
Key Research Accomplishments
10
Reportable Outcomes
10
Conclusion
10
References
11
Appendices
12-20
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