The Role of EBV Infection and Epigenetic Factors in Radioresistance of Colorectal Cancer.

Despite great progress made in therapeutic strategies, the 5-year survival rate of colorectal cancer (CRC) remains low due to the high incidence rate and mortality. A pivotal factor in treatment failure is radioresistance-the ability of CRC cells to withstand high doses of ionizing radiation (IR). Understanding the cellular and molecular mechanisms that underline radiation resistance as well as characteristics of radioresistant cells is particularly warranted for exploiting novel treatment modalities. In the context of combating radioresistance in CRC, potential targets of interest include Epstein-Barr virus (EBV), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and their related signaling pathways amenable to pharmacological intervention. Additionally, radiotherapy reprograms the tumor microenvironment that has impacts on innate and adaptive immunity, such as recruitment of cancer-associated fibroblasts (CAFs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). Targeting these immunosuppressive cells has the potential to enhance treatment responses in patients with radioresistant CRC. This review endeavors to depict a comprehensive landscape of factors influencing radiosensitivity of CRC, paving the way for advancements in future clinical applications.