**1. Introduction**

Extracellular vesicles (EVs) are a varied group of cell-derived, microscopic, fluid-filled pouches that cells release into the neighboring microenvironment. Recent studies show that not only do EVs play an integral part in the development of cancer through intercellular communication, cell survival, and immune modulation but also may assist with the early diagnosis and improved treatment of diseases such as epithelial ovarian cancer (EOC) [1]. EVs are quickly gaining recognition as an important enabler of EOC propagation and may potentially serve as a powerful tool in inhibiting and even reversing the progression of this disease. Historically, EOC has been a frustrating gynecologic malignancy characterized by its furtive early course that leads to an advanced presentation at initial diagnosis with subsequent poor outcomes [1]. Public health entities are ineffective at screening for early disease, leaving patients with few warnings to herald a lurking predator that affects 1–3% of women throughout their lifetime [2]. Once an EOC has manifested, the primary treatment options are surgery in combination with chemotherapy. While initially effective, these treatments are often fruitless at abating the malignancy due to the persistence of microscopic disease and the development of chemoresistance [3]. EOC patients desperately need new treatments, and EVs may provide an opportunity to gain an improved understanding about EOC proliferation and metastasis while hopefully providing novel, effective treatments.

### **1.1 Why is epithelial ovarian cancer so hard to treat, and how can EVs help?**

Worldwide, ovarian cancer is the seventh most common malignancy among women; and over 280,000 cases were diagnosed in 2012 alone [1, 4]. In the United States ovarian cancer is the fifth deadliest cancer among women and is the deadliest cancer originating in the female reproductive system [2]. The most common type of ovarian cancer is EOC, making up more than 90% of cases [5]. EOC encompasses numerous histologic subtypes, including serous, mucinous, endometrioid, and clear cell types; additionally, EOC can proliferate rapidly, known as high-grade disease, or have a more insidious course, known as low-grade disease [6]. Interestingly, in the past decade researchers discovered that high-grade serous EOC originates in the fallopian tubes and then migrates to the ovary; so clinicians treat EOC and fallopian tube cancer as the same entity [7]. Additionally, high-grade serous fallopian tube, ovarian, and primary peritoneal cancer are all considered the same clinical entity based on common behaviors and treatments [8]. The chapter will primarily discuss high-grade epithelial ovarian carcinoma of the ovary, fallopian tubes, and peritoneum because it is the predominant subtype of EOC and because publications prioritize this subtype when studying EVs.

EOC is a difficult disease. When testing detects this malignancy at an early stage, 80% of these patients are free of cancer at 5 years [8]. However, the early signs of EOC are nonspecific and insidious, ranging from abdominal discomfort or pain to bloating and early satiety [1]. Unfortunately, these vague symptoms lead to a late diagnosis for most patients, with about 80% of patients diagnosed with advanced disease that is more challenging to cure [9]. While surgery and chemotherapy are initially effective in treating advanced EOC, most patients experience a relapse of the cancer that is chemoresistant, with a five-year survival under 30% [5]. Based on these grim outcomes, patients need new diagnostic and therapeutic tools to improve detection and treatment of EOC.
