**4. Role of EVs in the prognosis of epithelial ovarian cancer**

EVs are positioned to provide valuable prognostic information for EOC because current prognostic tools struggle to accurately predict an individual's disease course and response to treatments. If there was a better understanding of how a patient's particular cancer would grow and which medicines would be effective against it, providers would better optimize treatment strategies that would extend a patient's life and even grant a better opportunity for cure. Currently, the prognosis for EOC is estimated based on generalized characteristics about this disease process within the context of the patient's health status and medical history [8]. Some factors include age, stage of the cancer at the time of diagnosis, and performance status [8]. In recent years genetic research has played a significant role in patient prognosis. BRCA mutations, a pathologic process that affects the repair of double-strand DNA breaks, place patients at increased lifetime risk for EOC but also confer an improved prognosis for EOC especially with new therapies that are targeted toward patients with these mutations. While these factors provide some helpful guidance regarding a patient's treatment outcomes, neither providers nor patients can accurately predict how an individual patient's EOC will respond to therapies. However, with EVs new factors are being identified that can help in better understanding which patients will respond to certain therapies and what personalized treatment regimens will best address the cancer.

An important part of caring for patients with EOC is selecting the best treatment for their specific tumor. When determining a patient's clinical management, the available prognostic information offers limited value in guiding clinicians about how to best care for their patients. However, novel therapeutic agents are demonstrating the need for refined prognostic tools that can identify a particular tumor's sensitivity or resistance to certain treatments. For example, the breakthrough use of PARP inhibitors for the treatment of EOC over the past decade served as an important demonstration of the necessity to discover new patient factors that facilitate targeted treatments [23]. In cancer cells with impaired repair of double-stranded DNA breaks, also known as homologous recombination deficiency (HRD), PARP inhibitors promote doublestranded breaks through the inhibition of secondary single-stranded DNA repair that triggers apoptosis [23]. When EOC with HRD is treated with a PARP inhibitor, these patients experience a significant improvement in the management of their cancer. Therefore, patients with EOC are now tested for homologous recombination

#### *Extracellular Vesicles and Ovarian Cancer DOI: http://dx.doi.org/10.5772/intechopen.101412*

deficiency [23]. While PARP inhibitors are clearly a success, patients need new biomarkers for individualized treatments; and EVs can be these new targets.

EOC quickly becomes resistant to front-line chemotherapy regimens, but it is currently not possible to predict which patients will develop chemoresistance [16]. Evidence from multiple studies suggest that EVs can predict which patients will have a tumor that is sensitive to chemotherapy [1]. For example, Yan studied a cohort of 50 patients and demonstrated an increase in serum EV annexin A3 levels, a protein involved in exocytosis and vesicle trafficking, among patients with resistance against primary chemotherapy drugs when compared to patients that are still sensitive to those chemotherapies [24]. In a second study protein RAB7A functioned as a potential mediator of chemoresistance [25]. Functioning as a key regulator of the influx of chemotherapy agents into cells, RAB7A is downregulated in chemoresistant cells, potentially affecting drug sequestration [25]. Finally, some groups are studying serum panels of EV miRNAs that are associated with chemoresistance and include miR-181a, miR-1908, miR-21, miR-486, and miR-223 [22]. Together, these different EV molecular targets may serve as prognostic biomarkers to identify chemoresistance in patients with EOC and help tailor the appropriate medication combination for each patient.
