**3. Roles of exosomes in common malignant diseases**

#### **3.1 Breast cancer**

Early diagnosis of breast cancer increases the chances of cure and survival. Although, mammography is widely used, it is difficult to detect cancers in women with dense mammary gland tissue when using this method [27], and unnecessary radiated exposure should be avoided. Blood, nipple suction fluid, sweat, urine, and tears are being investigated as alternative diagnostic methods; among these, urine and tear tests have relatively high sensitivity and specificity. For example, the urinary miRNA profile in patients with primary breast cancer is different from that in healthy controls [28–30]. Cala et al. identified cancer-specific patterns and constructed models for the early diagnosis of breast cancer. They found that a combination of succinic acid and dimethylheptanoyl carnitine was able to separate patients with breast cancer (n = 31) from healthy controls (n = 29) with a sensitivity of 93.5% and a specificity of 86.2% [29].

Currently, reported urinary biomarkers of breast cancer are still in the discovery stage, and their specificity and sensitivity need to be verified in cohort studies. There are also multiple reports of biomarkers in tears [31–35], which are relatively easy to obtain using non-invasive methods. Inubushi et al. compared the exosomes in tears from five women with metastatic breast cancer with those from eight healthy volunteers and found higher amounts of exosome markers in tears than in serum and higher expression of breast cancer-specific miR-21 and miR-200c in tears from the patients with metastatic breast cancer [35]. Therefore, exosomes in tears could also be a useful diagnostic and prognostic biomarker.

Drug resistance is also a factor that affects prognosis. The role of exosomes in drug resistance has received a great deal of attention. There are numerous reports on the association between exosomes and drug resistance in breast cancer [36–43]. Biomarkers can be used to predict the response of a tumor to a particular treatment and may reflect tumor susceptibility and drug resistance. Although, few methods are currently recommended for routine clinical application, blood-based monitoring of the therapeutic response is a minimally invasive and promising technique. Based on those methods, liquid biopsy analysis may bring novel information as biomarkers of breast cancer [44, 45].

#### **3.2 Prostate cancer**

Prostate cancer is a tumor with a high mortality rate, and early diagnosis has a significant effect on the prognosis. Serum and urinary exosomes are promising non-invasive biomarkers that could aid in early diagnosis [46–48]. Prostate cancer has a good prognosis when hormone therapy is effective, but castrate-resistant prostate

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

cancer has a markedly worse prognosis. Hessvik et al. identified 36 exosomal miRNAs as candidate biomarkers for prostate cancer in clinical studies [49]. Moreover, plasma miR-1290 and miR-375 levels correlate with reduced overall survival and have been identified as potential prognostic biomarkers of castrate-resistant prostate cancer [50, 51]. Expression of AR-V7 RNA in circulating tumor cells was identified as a predictor of the response to enzalutamide (an anti-androgen) and abiraterone (an anti-androgen and CYP17 inhibitor) in prostate cancer [52]. Del Re et al. detected the AR-V7 transcript preferentially in patients resistant to treatment with enzalutamide or abiraterone and proposed that the level of the AR-V7 transcript measured in extracellular vesicles in plasma could serve as a biomarker [53].

#### **3.3 Lung cancer**

Screening with low-dose CT is currently used for early diagnosis of lung cancer but is associated with radiation exposure. miRNAs derived from exosomes in body fluids are stable and relatively easy to obtain. Therefore, they are expected to be useful biomarkers for the early diagnosis of lung cancer [54–61]. Asakura et al. reported that serum miR-1268b and miR-6075 expression levels showed 99% sensitivity and 99% specificity for the diagnosis of lung cancer regardless of histological type or TNM stage [61]. This finding may lead to significant improvements in the results of screening for lung cancer and selection of more effective treatment for non-small cell lung cancer (NSCLC). Lebanony et al. reported that expression of exosomal miR-205 can distinguish between squamous and non-flat epithelial lung cancer even in poorly differentiated tumors [60]. Biomarkers that can predict the progression of lung cancer are also being investigated. Downregulation of miR-503 relative to non-malignant lung tissue has been observed in NSCLC tissue. For example, Liu et al. reported a link between the miR-503 level and advanced tumor stage and a poor prognosis [62]. These findings indicate that miR-503 may be a useful biomarker of survival in patients with NSCLC.
