Dissertations and Theses (Open Access)

Author ORCID Identifier

0000-0002-7705-7967

Date of Graduation

5-2026

Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Anil Sood, MD

Committee Member

Wendy Woodward, MD, PhD

Committee Member

Robert Dantzer, DVM, PhD

Committee Member

Nicholas Justice, PhD

Committee Member

Jinsong Liu, MD, PhD

Abstract

Patients with epithelial ovarian cancer (EOC) are known to experience hypothalamic-pituitary-adrenal (HPA) axis disturbances. Our group has previously shown that patients with EOC have elevated night-time cortisol levels, and that high cortisol levels correlate with shorter survival. We have shown that cortisol levels normalize in patients following cytoreductive surgery; given that studies have shown evidence of tumor-intrinsic hormone production in other cancer types, we wanted to investigate whether tumor-intrinsic glucocorticoid production is possible within ovarian cancer. In this study, the enzyme, 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is studied as a potential source of tumor intrinsic glucocorticoids, using a combination of bioinformatics analyses, in vitro experiments, and mouse models of. 11beta-HSD1 is expressed in a subpopulation of cancer-associated fibroblasts (CAFs) that are enriched in expression of pathways related to inflammation. Lab experiments show that 11beta-HSD1 activity can activate GR signaling. In animal models, 11beta-HSD1 silencing leads to tumor growth inhibition of a syngeneic ovarian cancer mouse model, changes in immune cell activation, and compensatory systemic increases in glucocorticoids. This work increases our understanding of glucocorticoid production in the setting of ovarian cancer and reveals a potential novel therapeutic target to improve efficacy of immunotherapy in ovarian cancer.

Keywords

Ovarian cancer, glucocorticoids, HPA axis

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Available for download on Wednesday, May 05, 2027

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