Huda Issa Atiya, PhD; University of Pittsburgh
Project Title: Endometriotic stromal changes as drivers of ovarian clear cell carcinoma initiation
Project Summary
It is known that survival rates for ovarian cancer are higher when the disease is detected early. Ovarian cancer has various subtypes; however, the field has primarily focused on detecting the most common type, high-grade serous ovarian cancer. Therefore, there is an unmet need to study other subtypes of ovarian cancer. Ovarian clear cell carcinoma (OCCC) is a rare but aggressive and chemo-resistant subtype. When diagnosed at an advanced stage, OCCC has poorer survival rates compared to stage-matched high-grade serous ovarian cancer. OCCC originates from a unique cell thought to arise from endometriosis. Endometriosis is a chronic inflammatory condition that affects 6-10% of reproductive-aged women in the U.S. It is a significant risk factor for developing OCCC; women with endometriosis are four times more likely to develop ovarian cancer than those without the condition. Thus, understanding how endometriosis transitions into OCCC will be essential for developing effective early detection tools and targeted treatments to prevent this progression.
We will study the contributions of endometriosis tissue in supporting OCCC initiation through iron regulation. Iron is critical for cell growth; however, iron overload can cause DNA damage and, consequently, lead to carcinogenesis. This work aims to understand how the endometriosis stromal microenvironment supports OCCC transformation. This research has the potential for significant clinical impact, as it can identify a stromal biomarker for OCCC initiation. Furthermore, this study could help pinpoint new targets to disrupt the formation or progression of OCCC.
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