Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. For patients who are resistant to monotherapy, multimodal therapy is a basic oncologic principle that incorporates surgery, radiotherapy (RT), and chemotherapy providing survival benefits for patients with most types of cancer. Although liver has low tolerance for radiation, high-precision RT for local HCC minimizes the likelihood of radiation-induced liver disease (RILD) in noncancerous liver tissue. RT have several therapeutic benefits, including the down-staging of tumors to make them resectable and repression of metastasis. The DNA damage response (DDR) is a cellular response to irradiation (IR), including DNA repair of injured cells and induction of programmed cell death, thereby resulting in maintenance of cell homeostasis. Molecules that block the activity of proteins in DDR pathways have been found to enhance radiotherapeutic effects. These molecules include antibodies, kinase inhibitors, siRNAs and miRNAs. MicroRNAs (miRNAs) are short non-coding regulatory RNAs binding to the 3′-untranslated regions (3′-UTR) of the messenger RNAs (mRNAs) of target genes, regulating their translation and expression of proteins. Thus, miRNAs and their target genes constitute complicated interactive networks, which interact with other molecules during carcinogenesis. Due to their promising roles in carcinogenesis, miRNAs were shown to be the potential factors that mediated radiosensitivity and optimized outcomes of the combination of systemic therapy and radiotherapy.
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