Ovarian cancer has an extremely high mortality rate due it its late stage of diagnosis. Characterizing molecular events of the early precursor lesions and the stem cell niche is a first and necessary step to generating novel strategies for early detection, chemoprevention and surgical intervention in the natural history of these neoplasms. Hence, the proposed study aims at addressing a fundamental question in ovarian tumor development which is defining the molecular signature of precursor lesions and tumor initiating cells in ovarian cancer. Towards this, we are using genome-wide approaches to determine the expression of noncoding RNAs and will further determine their expression in serum in order to evaluate them as biomarkers for early detection. This is the first time that a unique murine model of ovarian cancer is being used to comprehensively characterize the changes in miRNA expression through various stages of tumor progression. This project will make a significant impact on identifying new molecular pathways for early diagnosis, which is critical in reducing the disease mortality and chemoprevention. In summary, successful completion of the proposed study would lead not only to better early detection but also development of chemopreventative methods, which could significantly impact the current prognosis of ovarian cancer patients.

Public Health Relevance

The dismal prognosis in ovarian cancer is due to its diagnosis at an advanced stage. The rapid rate of tumor progression precludes identification of early changes that are critical for early diagnosis. We have generated a mouse model of ovarian cancer that accurately mimics ovarian cancer progression seen in humans. We propose to use this model to understand early changes that occur during tumor progression and further assess if these can be used to inform the development of a noninvasive serum-based test for early detection.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Research Grants (R03)
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Special Emphasis Panel (ZCA1)
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Wang, Wendy
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Brigham and Women's Hospital
United States
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Tucker, Douglass W; Getchell, Christopher R; McCarthy, Eric T et al. (2018) Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer. Clin Cancer Res 24:1389-1401
Li, Jie; Kuang, Yi; Shi, Junfeng et al. (2015) Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells. Angew Chem Int Ed Engl 54:13307-11
Hasan, Noor; Ohman, Anders W; Dinulescu, Daniela M (2015) The promise and challenge of ovarian cancer models. Transl Cancer Res 4:14-28