Abstract
Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.
Highlights
Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea; Abstract: therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy
It is used for treating metastatic CRC harboring wild type KRAS, which encodes a small G protein involved in the epidermal growth factor receptor (EGFR) pathway [65,79]
Drug resistance is considered a major obstacle in treating cancer
Summary
Colorectal cancer (CRC) occurs in both men and women, and there were 1.8 million cases worldwide in 2018, that resulted in approximately 880,800 deaths [1,2,3]. These immune checkpoint blockade agents have shown potent antitumor activity by increasing intra-tumoral T-cell penetration and by activating and upregulating PD-1/PD-L1 expression in a preclinical model [13,14,15] Despite these medical advances, chemotherapy, targeted therapy, and immunotherapy have shown a high rate of failure. This may be caused by invasion and metastasis of cancer-related drug resistance, resulting in decreased patient survival. MicroRNAs (miRNAs) are small non-coding RNAs that were first discovered in Caenorhabditis elegans They are involved in most biological processes, including development, differentiation, proliferation, growth, and apoptosis, as they finely regulate the expression of target genes [2,16,17]. We summarized the current knowledge on drug resistance-related miRNAs and their target genes with molecular mechanisms of acquired drug resistance and proposed novel strategies to overcome anti-cancer drug resistance
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