**Abstract**

Extracellular vesicles (EVs) represent a generic term for all the secreted vesicles, which include exosomes, microvesicles, and apoptotic bodies. EVs are key partners in the intercellular communication and play an essential role in multiple physiological and pathological conditions. EVs are shuttles for cargo molecules, such as RNA (mRNA, microRNA, and other noncoding RNAs), DNA, proteins (receptors, transcription factors, enzymes, and extracellular matrix proteins), and lipids. In pathological states, including cancer, EVs might represent either useful biomarkers or can be used for therapeutic purposes. Moreover, in cancer, it was demonstrated that EVs play an essential role in drug resistance. Here, we review the role played by EVs in the most common forms of cancer, with a special focus on ovarian and breast cancers.

**Keywords:** extracellular vesicles, cancer, biomarker, cargo, therapy

### **1. Introduction**

Extracellular vesicles (EVs) are cell-derived membranous vesicles (from normal or cancerous cells) bearing packages of information within or on their surface. Their content can influence neighboring or remote cells, and therefore, EVs are considered to play an important role in intercellular communication [1]. Different functional molecules (proteins, mRNA, and microRNAs) are transferred between cells with the aid of EVs. The content of EVs is highly variable and dependent of the cell of origin. The EVs in human blood originate from platelets, leukocytes, erythrocytes, endothelial cells, vascular smooth muscle cells, and cancer cells (for review see [2]). It is now widely accepted that extracellular vesicles also represent a potential resource for biomarkers.

The first study suggesting the existence of extracellular vesicles was carried out in 1946 [3]. In a 1967 report, membrane particles derived from activated platelets, termed "platelet dust," were commonly considered as a waste product or cellular debris directly budded from the plasma membrane [4]. Both prokaryotes and higher eukaryotes can release EVs. Different terms are used to describe EVs due to varying methods of isolation and due to the biogenesis mechanism. The terminologies of EVs include microvesicles, dexosomes, texosomes, archaeosomes, argosomes, prostasomes, epididymosomes, and oncosomes [5]. Gradually, while building up knowledge about EVs, a need for its classification emerged and the International Society for Extracellular Vesicles (ISEV) was founded [6]. This society provided some criteria to classify EVs into three groups: microvesicles (MVs), exosomes, and apoptotic bodies (for details visit www.isev.org). These vesicles are secreted by both normal cells and cancerous cells as means of cell-to-cell communication. Alternatively, they may be prepared artificially from the engineered artificial lipid vesicles called liposomes in which EVs' features, components, or cargos are incorporated and are the most likely to be useful for drug delivery [7].

EVs are actively involved in cell-to-cell communication, inflammation, chronic disease development and progression, pre-metastatic niche formation, and the metastatic organotropism of different tumor types [8]. Tumor-derived EVs (TEVs) have been reported to play major roles in the onset, progression, and metastasis of cancer, including ovarian [9], breast [10], colorectal [11, 12], prostate cancer [13], and melanoma [14–16].

Here, we review knowledge about EVs in cancer, with a focus on breast and ovarian cancers. We discuss the importance of the content of EVs (e.g., nucleic acids, and proteins) in cancer development, metastasis, and drug resistance.
