*4.3.1 Chemotherapy*

Although there are advances in cytotoxic and targeted therapy in CRC, drug resistance is one of the most important obstacles in front of successful chemotherapy [89]. Fluoropyrimidine-based chemotherapy (5-FU or capecitabine), vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted, and epidermal growth factor receptor (EGFR)-targeted therapies are the main therapeutic methods for CRC [87]. miRNAs have role in chemotherapy resistance in terms of deregulation of drug metabolism-related enzymes, increased efflux of chemotherapeutics, impairment of chemotherapeutic-induced apoptosis, modulation of DNA damage repair, and autophagy [87].

miR-92b-3p, miR-3156-5p, miR-10a-5p, and miR-125a-5 were found to be related with progression-free survival in meta;static CRC patients treated with 5-FU/oxaliplatin/bevacizumab regime [90]. A negative relationship was found between miR-27b, miR-148a, and miR-326 expression levels and progression-free survival in metastatic colorectal cancer patients receiving first-line oxaliplatinbased treatment [91]. The expression of miR-326 was related with decreased overall survival. These results proposed that plasma miRNAs can be used as noninvasive biomarkers for evaluating drug response in metastatic CRC patients who are treated with 5-FU and oxaliplatin-based chemotherapy [91] (**Table 2**).
