Exosomal Cargo-Derived Mediators of Ovarian Cancer Chemoresistance

Exosomes are small extracellular vesicles secreted by various cells. They play a vital role in intercellular communication due to their diverse molecular cargo. Recent advancements in biomedical research have enabled a more detailed characterization of exosomes and their significant role in cancer biology, particularly in understanding mechanisms that contribute to chemoresistance. This review focuses on the current understanding of exosomes in ovarian cancer, one of the deadliest gynecological malignancies, known for its high recurrence and treatment failure rates. Chemoresistance in ovarian cancer stems from several factors, including altered drug efflux, enhanced DNA repair mechanisms, changes in the tumor microenvironment, and modifications in signaling pathways. Emerging evidence suggests that exosomes facilitate these processes by transferring regulatory molecules such as proteins, microRNAs (miRNAs), and circular RNAs (circRNAs) between cells, which in turn modulate drug response and tumor progression. For instance, exosomal proteins such as DNA methyltransferase 1 (DNMT1) and circular forkhead box P1 (circFoxp1), along with miRNAs like miR-21-3p, miR-1246, and miR-6836, have been associated with promoting resistance to platinum- and taxane-based chemotherapies. Conversely, some exosomal miRNAs, including miR-30a-5p, may enhance drug sensitivity. Furthermore, circRNAs transported by exosomes, such as hsa_circ_0010467, circ-PIP5K1A, and circ_0025033, play a role in regulating key oncogenic pathways associated with chemoresistance. Overall, these findings highlight the multifaceted role of exosomes in ovarian cancer biology and underscore their potential as both biomarkers and therapeutic targets. A deeper understanding of how exosomes mediate molecular mechanisms may lead to novel strategies for overcoming chemoresistance and improving treatment outcomes for ovarian cancer patients.