Targeting RNA splicing modulation: new perspectives for anticancer strategy?

IF 12.8 1区 医学 Q1 ONCOLOGY Journal of Experimental & Clinical Cancer Research Pub Date : 2025-01-30 DOI:10.1186/s13046-025-03279-w
Xuemei Lv, Xiaoyu Sun, Yang Gao, Xinyue Song, Xiaoyun Hu, Lang Gong, Li Han, Miao He, Minjie Wei
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Abstract

The excision of introns from pre-mRNA is a crucial process in the expression of the majority of genes. Alternative splicing allows a single gene to generate diverse mRNA and protein products. Aberrant RNA splicing is recognized as a molecular characteristic present in almost all types of tumors. Therefore, identifying cancer-specific subtypes from aberrant processing offers new opportunities for therapeutic development. Numerous splicing modulators, each utilizing different mechanisms, have been developed as promising anticancer therapies, some of which are in clinical trials. In this review, we summarize the splice-altered signatures of cancer cell transcriptomes and the contributions of splicing aberrations to tumorigenesis and progression. Especially, we discuss current and emerging RNA splicing-targeted strategies for cancer therapy, including pharmacological approaches and splice-switching antisense oligonucleotides (ASOs). Finally, we address the challenges and opportunities in translating these findings into clinical practice.

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靶向RNA剪接调节:抗癌策略的新视角?
从pre-mRNA中去除内含子是大多数基因表达的关键过程。选择性剪接允许单个基因产生多种mRNA和蛋白质产物。异常RNA剪接被认为是几乎所有类型肿瘤中存在的分子特征。因此,从异常加工中识别癌症特异性亚型为治疗发展提供了新的机会。许多剪接调节剂,每一个利用不同的机制,已经发展成为有前途的抗癌疗法,其中一些是在临床试验。在这篇综述中,我们总结了癌细胞转录组剪接改变的特征以及剪接畸变对肿瘤发生和发展的贡献。特别地,我们讨论了当前和新兴的RNA剪接靶向癌症治疗策略,包括药理学方法和剪接开关反义寡核苷酸(ASOs)。最后,我们讨论了将这些发现转化为临床实践的挑战和机遇。
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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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