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Archive > Volume 32 Issue 4 > 2025,32(4):347-355. DOI:10.3872/j.issn.1007-385X.2025.04.001 Prev Next
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Current situation and challenges of tumor biotherapy based on alternative splicing
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Abstract:
[Abstract] Alternative splicing, a post-transcriptional regulatory mechanism of gene expression, contributes to the diversity of the transcriptome and proteome in eukaryotes. However, aberrant alternative splicing serves as a significant driver of tumor progression, where abnormal splicing in tumor cells, immune cells, and other cell types within the tumor microenvironment collectively results in malignant behaviors of cancer cells, immune evasion, and the immunosuppressive milieu that supports tumor advancement. Targeting tumor-associated spliceosomes, splicing regulatory factors, splicing isoforms and variants, as well as tumor neoantigens generated by aberrant alternative splicing, has emerged as a novel strategy in cancer biotherapy. Some alternative splicing-based antitumor biotherapy programs have progressed to phase Ⅰ clinical trials. Alternative splicing-based tumor therapy still faces scientific and technological challenges such as safety, optimization of long-read sequencing and bioinformatics algorithm, and nucleic acid drug delivery. Addressing these challenges will provide new tumor therapy strategies and open up new frontiers for precisely screening tumor-related targets and highly immunogenic neoantigens, overcoming drug resistance in traditional therapies, and enhancing the efficacy of immune checkpoint blockade, CAR-T cell therapy, and other treatments.
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