We propose to create a Clinical Validation Center within the Early Detection Research Network that is focused on breast and gynecologic cancers. Our group brings a combination of depth of experience and clinical resources that would be difficult to match. This Center will be comprised of two primary sites: Duke University Medical Center (DUMC) and Johns Hopkins Medical Institute (JHMI). Each of these sites will contribute clinical resources including specimens and data and will collaborate and coordinate on biomarker validation trials. The primary mission of our group will be to compare promising biomarkers for their utility in specific clinical applications for breast, ovarian, and cervical cancer. We propose that this will include studies of overall risk, early detection, likelihood of disease progression, and disease monitoring. We not expect that all such studies will be performed for all diseases;however we are prepared to perform several such studies at the onset of the program. These studies include markers of high risk lesions in cervical dysplasia, markers of progression in pre-invasive breast cancer, and predictors of outcome in serous ovarian cancer. The resources that we will use to accomplish these goals include: 1) High and consistent patient volume and subject recruitment, 2) Large and mature collections of clinical specimens including serum, plasma, DNA, and tissue all linked and updated regularly, 3) Large subsets of specimens are already annotated with molecular data including gene expression, CGH, SNP, methylation, and proteomic analyses, 4) A large population based case control study in ovarian cancer, 5) Access to other large data and clinical resources including the Ovarian Cancer Association Consortium and first contributor information from The Cancer Genome Atlas (TCGA) for both breast and ovarian cancer. Our expertise comes from biomarker discovery and development in these diseases and is augmented by the various rigors of population science, statistics, and clinical research. Our Center will also participate fully in all activities of the Network and seek additional collaborations within and outside the Network as needed to advance the work.

Public Health Relevance

The Clinical Validation Center will test new markers and approaches for the early detection of breast and gynecologic cancers. This is instrumental in developing strategies to target populations most at risk of disease for efficient detection and diagnosis. The work of this Center will also be critical for informing policy discussions and recommendations as we contemplate introduction of new screening modalities for these common and life threatening diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA084955-14
Application #
8505386
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (M1))
Program Officer
Rinaudo, Jo Ann S
Project Start
1999-09-30
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
14
Fiscal Year
2013
Total Cost
$468,371
Indirect Cost
$168,133
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Marks, Jeffrey R; Anderson, Karen S; Engstrom, Paul et al. (2015) Construction and analysis of the NCI-EDRN breast cancer reference set for circulating markers of disease. Cancer Epidemiol Biomarkers Prev 24:435-41
Tang, Xiaohu; Lin, Chao-Chieh; Spasojevic, Ivan et al. (2014) A joint analysis of metabolomics and genetics of breast cancer. Breast Cancer Res 16:415
Wolf, Omer; Weissman, Oren; Harats, Moti et al. (2013) Birth wind and fire: raising awareness to operating room fires during delivery. J Matern Fetal Neonatal Med 26:1303-5
Sfakianos, Gregory P; Iversen, Edwin S; Whitaker, Regina et al. (2013) Validation of ovarian cancer gene expression signatures for survival and subtype in formalin fixed paraffin embedded tissues. Gynecol Oncol 129:159-64
Schildkraut, Joellen M; Iversen, Edwin S; Akushevich, Lucy et al. (2013) Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev 22:1709-21
Jin, Hongjun; Daly, Don S; Marks, Jeffrey R et al. (2013) Oxidatively modified proteins as plasma biomarkers in breast cancer. Cancer Biomark 13:193-200
Wardell, Suzanne E; Marks, Jeffrey R; McDonnell, Donald P (2011) The turnover of estrogen receptor ? by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy. Biochem Pharmacol 82:122-30
Liggett, Thomas E; Melnikov, Anatoliy A; Marks, Jeffrey R et al. (2011) Methylation patterns in cell-free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients. Int J Cancer 128:492-9
Kung, Hsiu-Ni; Marks, Jeffrey R; Chi, Jen-Tsan (2011) Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia. PLoS Genet 7:e1002229
Gatza, Michael L; Kung, Hsiu-Ni; Blackwell, Kimberly L et al. (2011) Analysis of tumor environmental response and oncogenic pathway activation identifies distinct basal and luminal features in HER2-related breast tumor subtypes. Breast Cancer Res 13:R62

Showing the most recent 10 out of 24 publications