Deng Kun, Yao Jingwei, Huang Jialu, Ding Yubo, Zuo Jianhong
The Laboratory of translational medicine, Hengyang Medical School, University of South China, 28 Changsheng Road, Hengyang, Hunan 421001, P R China.
The Affiliated Nanhua Hospital of University of South China, Hengyang, Hunan 421002, P R China.
Transl Oncol. 2021 Jun;14(6):101077. doi: 10.1016/j.tranon.2021.101077. Epub 2021 Mar 26.
Abnormally alternative splicing events are common hallmark of diverse types of cancers. Splicing variants with aberrant functions play an important role in cancer development. Most importantly, a growing body of evidence has supported that alternative splicing might play a significant role in the therapeutic resistance of tumors. Targeted therapy and immunotherapy are the future directions of tumor therapy; however, the loss of antigen targets on the tumor cells surface and alterations in drug efficacy have resulted in the failure of targeted therapy and immunotherapy. Interestingly, abnormal alternative splicing, as a strategy to regulate gene expression, is reportedly involved in the reprogramming of cell signaling pathways and epitopes on the tumor cell surface by changing splicing patterns of genes, thus rendering tumors resisted to targeted therapy and immunotherapy. Accordingly, increased knowledge regarding abnormal alternative splicing in tumors may help predict therapeutic resistance during targeted therapy and immunotherapy and lead to novel therapeutic approaches in cancer. Herein, we provide a brief synopsis of abnormal alternative splicing events in cancer progression and therapeutic resistance.
异常的可变剪接事件是多种类型癌症的常见特征。具有异常功能的剪接变体在癌症发展中起重要作用。最重要的是，越来越多的证据支持可变剪接可能在肿瘤的治疗抗性中起重要作用。靶向治疗和免疫治疗是肿瘤治疗的未来方向；然而，肿瘤细胞表面抗原靶点的丧失和药物疗效的改变导致了靶向治疗和免疫治疗的失败。有趣的是，异常可变剪接作为一种调节基因表达的策略，据报道通过改变基因的剪接模式参与细胞信号通路和肿瘤细胞表面表位的重编程，从而使肿瘤对靶向治疗和免疫治疗产生抗性。因此，增加对肿瘤中异常可变剪接的了解可能有助于预测靶向治疗和免疫治疗期间的治疗抗性，并导致癌症的新治疗方法。在此，我们简要概述了癌症进展和治疗抗性中的异常可变剪接事件。
