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非编码RNA在结直肠癌化疗和放疗抗性中的作用

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

作者信息

Fanale Daniele, Castiglia Marta, Bazan Viviana, Russo Antonio

机构信息

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy.

出版信息

Adv Exp Med Biol. 2016;937:207-28. doi: 10.1007/978-3-319-42059-2_11.

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.

摘要

尽管近年来在理解癌症信号通路和开发新的治疗策略方面取得了进展,然而,结直肠癌(CRC)细胞对化疗和放疗的耐药性仍是成功治疗的主要障碍,导致肿瘤复发,进而预后不良。因此,克服耐药性和放射抗性,提高CRC细胞对药物和辐射的敏感性,以及提高化疗和放疗的疗效在CRC治疗中具有重要意义。鉴定能够预测治疗反应和预后的新分子生物标志物是药物基因组学和癌症研究中最重要的目标之一。最近的研究表明,非编码RNA(ncRNA),如微小RNA(miRNA)和长链非编码RNA(lncRNA),可能通过控制包括细胞周期、增殖、凋亡和DNA损伤修复在内的多种信号通路,在CRC的化疗和放疗抗性调节中发挥重要作用。最近的数据表明,对ncRNA活性的选择性调节可以改善对化疗和放疗的反应,提供一种基于ncRNA相关基因治疗的创新抗肿瘤方法。因此,ncRNA不仅可以作为预测和预后生物标志物,还可以作为开发克服CRC耐药性和放射抗性的新型治疗策略的靶点。在本章中,我们讨论了ncRNA在CRC化疗和放疗抗性中的作用,强调了这些分子在预测治疗反应和调整治疗方面的影响,并描述了这些过程中可能涉及的细胞内途径。

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