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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Physiology
First Advisor
Gil Mor
Second Advisor
Sorin Drăghici
Abstract
The 5-year survival rate for high grade serous ovarian cancer (HGSOC) is barely 30% because most patients are diagnosed late, and the cancer typically recurs even after initial successful treatment. Therefore, early detection and effective therapies to prevent (or at least, significantly delay) cancer recurrence are the two major unmet needs in HGSOC management. Although emerging evidence has now confirmed the Fallopian tubes as the site of origin of HGSOC, the exact mechanisms which underlie the early transformation of normal Fallopian tube into precursors of HGSOC, and their eventual progression to invasive and recurrent carcinoma are not fully understood. In this dissertation, we sought to understand the molecular mechanisms underlying ovarian cancer initiation and progression to help us identify novel early detection biomarkers and therapeutic targets for HGSOC. By performing spatial transcriptomic studies on normal and malignantly transformed Fallopian tube epithelium, we identified loss of Connective Tissue Growth Factor (CTGF) as a critical event during early malignant transformation of the Fallopian tube epithelium. Additionally, we observed the enrichment of inflammatory processes in the stroma of transformed Fallopian tube, underscoring the importance of dysregulated immune processes during ovarian cancer initiation and progression. Subsequently, we showed that successful chemotherapy reverses immunologic tolerance to cancer cells, re-establishing immune surveillance and anti-tumoral immune response in long-term responders compared to early recurrence patients. Overall, this dissertation lays important foundation for future work to facilitate development of effective early detection tests, improved patient stratification, and novel therapies to someday improve patient outcomes from this lethal malignancy.
Recommended Citation
Adzibolosu, Nicholas Korkuvi, "Immune Mechanisms In Ovarian Cancer Initiation And Progression: Implications For Early Detection And Novel Therapies." (2025). Wayne State University Dissertations. 4192.
https://digitalcommons.wayne.edu/oa_dissertations/4192