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Published on: May 30, 2025
Altered RNA Processing in Cancer Pathogenesis and Therapy
Esther A Obeng1, Connor Stewart2, Omar Abdel-Wahab3
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. abdelwao@mskcc.org esther.obeng@stjude.org.
Abstract:
Major advances in our understanding of cancer pathogenesis and therapy have come from efforts to catalog genomic alterations in cancer. A growing number of large-scale genomic studies have uncovered mutations that drive cancer by perturbing cotranscriptional and post-transcriptional regulation of gene expression. These include alterations that affect each phase of RNA processing, including splicing, transport, editing, and decay of messenger RNA. The discovery of these events illuminates a number of novel therapeutic vulnerabilities generated by aberrant RNA processing in cancer, several of which have progressed to clinical development. SIGNIFICANCE: There is increased recognition that genetic alterations affecting RNA splicing and polyadenylation are common in cancer and may generate novel therapeutic opportunities. Such mutations may occur within an individual gene or in RNA processing factors themselves, thereby influencing splicing of many downstream target genes. This review discusses the biological impact of these mutations on tumorigenesis and the therapeutic approaches targeting cells bearing these mutations.
Insights
Genomic alterations impact RNA processing in cancer, creating new therapeutic targets. Understanding these mutations in RNA splicing and polyadenylation is key to developing novel cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Genomic alterations are crucial for understanding cancer development and treatment.
- Large-scale genomic studies reveal mutations affecting RNA processing, including splicing, transport, editing, and decay.
- Aberrant RNA processing in cancer creates novel therapeutic vulnerabilities.
Purpose of the Study:
- To review the biological impact of genetic alterations in RNA processing on tumorigenesis.
- To discuss therapeutic strategies targeting cancer cells with mutations in RNA processing.
- To highlight the significance of RNA splicing and polyadenylation alterations in cancer.
Main Methods:
- Review of major genomic studies and literature on cancer pathogenesis and therapy.
- Analysis of mutations affecting cotranscriptional and post-transcriptional gene regulation.
- Discussion of clinical development of therapies targeting RNA processing defects.
Main Results:
- Genetic alterations affecting RNA splicing and polyadenylation are common in cancer.
- Mutations can occur within individual genes or RNA processing factors, impacting multiple downstream genes.
- Aberrant RNA processing presents novel therapeutic opportunities.
Conclusions:
- Understanding the role of RNA processing alterations in cancer is critical for identifying new therapeutic targets.
- Targeting RNA processing defects offers promising avenues for cancer treatment.
- Further research into the biological impact and therapeutic potential of these mutations is warranted.
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