A Promising Druggable Target for Translational Therapy of Ovarian Cancer: A Molecular Profiling of Therapeutic Innovations, Extracellular Vesicle Acquired Resistance, and Signaling Pathways

Abstract: Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related deaths in the United States, posing a significant threat to female health. Late-stage diagnoses, driven by elusive symptoms often masquerading as gastrointestinal issues, contribute to a concerning 70% of cases being identified in advanced stages. While early-stage OC brags a 90% cure rate, progression involving pelvic organs or extending beyond the peritoneal cavity drastically diminishes it. Overcoming chemoresistance and metastasis requires a deep understanding of the associated progression mechanisms for innovative therapies. Extracellular vesicles (EVs), containing proteins, RNAs, DNAs, and metabolites, have surged in recent years, significantly impacting tumor progression, recurrence, immune evasion, and metastasis associated with the ovarian tumor microenvironment. Recent research unveils organ-specific metastatic patterns in OC, providing insights into tumor cell interactions and signaling crosstalk with stromal cells. The review explores the role of EVs behind OC cell metastasis and chemoresistance. Furthermore, the article delves into the role of EVs in the tumor microenvironment, immune evasion, and as biomarkers in context to OC, offering promising therapeutic strategies to enhance survival rates for OC patients. Lastly, the article focuses on an overview of PI3K/AKT/mTOR, MAPK/ERK, and VEGFR signaling pathways in the pathophysiology of ovarian cancer.