**1. Introduction**

Approximately half of all patients with cancer receive radiation therapy as part of their treatment making it critical in the treatment of cancer [1]. Radiation therapy is used in curative and palliative regimens to achieve locoregional control [2]. Furthermore, radiation therapy is often combined with surgery, chemotherapy, and more recently, immunotherapy [3]. Despite the progress made in approaches to deliver radiation, precision medicine and combined therapies, resistance to treatment, and recurrence continue to occur in the clinical setting. According to recent studies, components of exosomes such as miRNAs and lncRNAs perpetuate drug resistance. In gastric cancer, it is reported that exosomes from M2-macrophageinduced miR-21 mediated upregulation of PI3K/Akt signaling and reduced apoptosis and cisplatin resistance [4]. In breast cancer, exosomal miR-221/222 modulated p27 and estrogen receptor (ER) for tamoxifen resistance, and exosomal cargo-lncRNA

UCA1 mediated tamoxifen resistance [5, 6]. In prostate cancer, cancer-associated fibroblast-derived exosomes conferred gemcitabine resistance via Snail and miR-146a [7].

Biologically, radiation induces damage to DNA and other host cell structures by oxidative stress [8]. Following exposure to X-rays, free radical production caused by the interaction of ionizing radiation with water molecules and redox-mediated biological pathways are responsible for oxidative DNA damage and cell death. Interaction of free radicals with DNA causes the formation of different types of DNA oxidation in both nucleus and mitochondria. Oxidation of DNA and also cell death through necrosis or apoptosis can stimulate inflammatory responses and oxidative stress, leading to further DNA damage. Oxidized cell-free DNA is elevated in cancer patients and also patients undergoing radiation therapy for their malignancies [9, 10].

Irradiated cells generate communication signals and cause biological changes in neighboring or distant non-irradiated cells. This phenomenon is known as the radiation-induced bystander effect (RIBE) [11, 12]. Although, the exact mechanism of RIBE remains unclear, there is increasing evidence to suggest that exosomal microRNAs (miRNAs) support various cellular regulatory roles in the response to radiation [13–15].

Radiation therapy has recently been shown to have systemic immune-modulating effects in patients with cancer, including an abscopal effect whereby local radiation elicits a systemic immune response and alleviates the tumor burden in untreated areas [16]. Although, the mechanism of the abscopal effect remains to be fully elucidated, there is accumulating evidence indicating a strong association between this effect and tumor-derived exosomes.

Exosomes are membrane vesicles with a diameter of 30–150 nm that are released by the fusion of an organelle in the endocytic pathway, the multivesicular body, and

#### **Figure 1.**

*Cancer-derived exosomes mediate various intercellular communications and induce the proliferation of cancer cells. Through communication with endothelial cells, vascular endothelial barriers are destroyed and metastasis is induced by cancer-derived exosomes. NK and CD8-positive cells are suppressed by cancer-derived exosomes. Macrophages are activated into M2 macrophages by cancer-derived exosomes. NK, natural killer.*

*Exosomes in Cancer Diagnosis and Radiation Therapy DOI: http://dx.doi.org/10.5772/intechopen.101684*

the plasma membrane [17]. Exosomes are released in a four-stage process, namely, initiation, endocytosis, formation of multivesicular bodies, and release of exosomes. The exosome with its cargo, consisting of messenger RNA (mRNA), miRNA, mitochondrial DNA (mtDNA), single-stranded DNA, double-stranded DNA, retrotransposons, and various proteins (MHC class I and II molecules, cytokines, adhesion molecules, transmembrane molecules, integrins, and tetraspanin) are released by the host cells and transferred to the recipient cells [18–20]. Exosomes are a subgroup of extracellular vesicles that are released by all types of cells, including tumor cells. Exosomes mediate intercellular communication by transporting various intracellular components, including cargos [21] and induce a variety of phenomena, including the proliferation of cancer cells [22], metastasis [23], and resistance to treatment [24]. Tumor-derived exosomes affect not only cancer cells themselves but also vascular endothelial cells and various types of immune cells (**Figure 1**). Exosomes released from tumor cells may affect proximal tumor cells and stromal cells in the local microenvironment and can also have systemic effects via their functional components, such as microRNAs and proteins, via the circulation. Emerging evidence suggests that tumor-derived exosomes have both immunostimulatory and immunosuppressive activity that depends on the molecules inside these structures and the status of immune cells in the tumor microenvironment [24, 25].
