The vast majority of cancer-related deaths are due to metastasis of the primary tumor that develops years to decades after apparent cures. However, it is difficult to effectively prevent or treat cancer metastasis. Recent studies have shown that communication between cancer cells and surrounding cells enables cancer progression and metastasis. The comprehensive term “extracellular vesicles” (EVs) describes lipid bilayer vesicles that are secreted to outside cells; EVs are well-established mediators of cell-to-cell communication. EVs participate in cancer progression and metastasis by transferring bioactive molecules, such as proteins and RNAs, including microRNAs (miRNAs), between cancer and various cells in local and distant microenvironments. Clinically, EVs functioning as diagnostic biomarkers, therapeutic targets, or even as anticancer drug-delivery vehicles have been emphasized as a result of their unique biological and pathophysiological characteristics. The potential therapeutic effects of EVs in cancer treatment are rapidly emerging and represent a new and important area of research. This review focuses on the therapeutic potential of EVs and discusses their utility for the inhibition of cancer progression, including metastasis.

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis. Bone is a preferred site of metastasis, and bone metastasis is generally incurable and dramatically affects patient quality of life. Bone metastasis can cause devastating complications, including hypercalcemia, pathological fractures, spinal compression, and bone pain, which result in a poor prognosis. Although the mechanisms underlying bone metastasis have yet to be fully elucidated, increasing evidence suggests that EVs in the bone microenvironment significantly contribute to cancer progression and cancer bone tropism. Emerging evidence on EV functions in bone metastasis will facilitate the discovery of novel treatments. In this review, we will discuss the remarkable effects of EVs, especially on the tumor microenvironment in bone.

Extracellular Vesicles and Circulating Nucleic Acids is an open access journal, focusing on extracellular vesicles and circulating nucleic acids including DNA, RNA, and miRNA and their therapeutic use.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Oral cancer is the sixth most common cancer worldwide, with approximately 530,000 new cases and 300,000 deaths each year. The process of carcinogenesis is complex, and survival rates have not changed significantly in recent decades. Early detection of cancer, prognosis prediction, treatment selection, and monitoring of progression are important to improve survival. With the recent significant advances in analytical technology, liquid biopsy has made it possible to achieve these goals. In this review, we report new results from clinical and cancer research applications of liquid biopsy, focusing on extracellular vesicles (EVs) among the major targets of liquid biopsy, namely, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and EVs. In addition, the potential application of EVs derived from gram-negative bacteria (outer membrane vesicles; OMVs) among oral bacteria, which have recently attracted much attention, to liquid biopsy for oral cancer will also be addressed.