Serous ovarian carcinoma is the most common and aggressive form of ovarian cancer. The 5 year survival rate for stage I ovarian cancer is >90%;however, stage I tumors (i.e., confined to the ovary) are more often the exception than the rule. Instead, most women (~75%) present with widely disseminated (stage III/IV) disease, for which the 5 year survival rate is a dismal 30% or less. Unfortunately, this statistic has not changed in over 3 decades. Furthermore, while most patients initially respond to standard chemotherapy, the majority ultimately relapse with chemo-resistant disease. The best tools available for detecting early-stage disease are transvaginal ultrasound and serum biomarker testing;however, neither is entirely specific and both can lead to false-positive results. In fact, no seru markers are currently FDA approved for early screening for ovarian cancer. Instead the 2 FDA approved serum biomarkers, CA125 and HE4, are only approved clinically for determining response to treatment and for detecting recurrence of disease. We recently reported that a novel protein, Elafin, is synthesized and secreted by ovarian tumor cells, and is highly expressed in subset of serous ovarian carcinomas. Importantly, unlike CA125 and HE4, patients whose tumors express Elafin have a poor overall survival. In addition, the Elafin protein is also expressed by a very aggressive form of breast cancer, called basal-like carcinoma, which occurs more frequently in younger, pre-menopausal women, including BRCA1 mutation carriers, where mammography is not as effective. Given that Elafin is secreted by these aggressive tumors, developing a test to detect it in the bloodstream would help clinicians triage patients for appropriate care and treatment, having the potential to improve morbidity and outcome. Therefore, the goals of this proposal are: 1) comprehensively examine Elafin expression in ovarian and breast cancers, including all subtypes of each disease as well as benign lesions, to determine whether Elafin expression is truly unique and specific to serous and basal-like carcinomas, and 2) to develop an antibody-based test to detect Elafin in the bloodstream of cancer patients. Characterization of Elafin in breast and ovarian cancers and the development of an Elafin blood test may significantly impact the clinical management of women with these cancers, their survival, and outcome.

Public Health Relevance

Ovarian cancer is called the silent killer because most patients present with wide-spread disseminated disease, and therefore have little to no chance for curative therapy. Much like ovarian cancer, basal-like carcinoma, an aggressive form of breast cancer, also has a poor survival rate and typically affects younger women. The ultimate purpose of this study is to develop a blood test that will detect a protein called Elafin, which is secreted by both ovarian and basal-like breast cancer cells, in hopes of identifying affected patients early in their disease course, thus greatly improving survival.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA156021-02
Application #
8604695
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Kim, Kelly Y
Project Start
2013-01-11
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$168,517
Indirect Cost
$42,282
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
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