Involvement of Non-coding RNAs in Chemo- and Radioresistance of Colorectal Cancer.

ABSTRACT

Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the efficacy of chemo- and radiotherapy have an important significance in the treatment of CRC. The identification of new molecular biomarkers which can predict therapy response and prognosis is one of the most significant aims in pharmacogenomics and cancer research.Recent studies showed that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), may play important roles in the regulation of chemo- and radioresistance of CRC, by controlling several signaling pathways, including cell cycle, proliferation, apoptosis and DNA damage repair. Recent data have demonstrated that selective modulation of the ncRNA activity can improve the response to chemo- and radiotherapy, providing an innovative anti-tumor approach based on a ncRNA-related gene therapy. Therefore, ncRNAs could not only be useful as predictive and prognostic biomarkers but also serve as targets for the development of novel therapeutic strategies to overcome drug and radiation resistance in CRC. In this chapter, we discuss the involvement of ncRNAs in chemo- and radiotherapy resistance of CRC, highlighting the impact of these molecules in prediction of the treatment response and modification of the therapy, and describing possible intracellular pathways involved in these processes.