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Updated: Feb 17, 2026
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer
Nidhi Jyotsana1, Michael Heuser1
1a Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation , Hannover Medical School , Hannover , Germany.
Introduction:
Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development. Expert opinion: Alternative splicing is an important mechanism that controls gene expression, and hence pharmacologic and genetic control of aberrant alternative RNA splicing has been proposed as a potential therapy in cancer. To identify and validate aberrant RNA splicing patterns as therapeutic targets we need to (1) characterize the most common genetic aberrations of the spliceosome and of splice sites, (2) understand the dysregulated downstream pathways and (3) exploit in-vivo disease models of aberrant splicing. Antisense oligonucleotides show promising activity, but will benefit from improved delivery tools. Inhibitors of mutated splicing factors require improved specificity, as alternative and aberrant splicing are often intertwined like two sides of the same coin. In summary, targeting aberrant splicing is an early but emerging field in cancer treatment.
Insights
Aberrant RNA splicing, driven by genetic mutations, is a hallmark of many cancers. Targeting these splicing defects offers a promising new avenue for cancer therapeutics.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in splicing-related genes and splice sites are implicated in both hematologic malignancies and solid cancers.
- Aberrant RNA splicing in cancer arises from direct genetic alterations in spliceosome components or mutations within oncogenes and tumor suppressor genes.
- Alternative splicing is a critical regulator of gene expression, and its dysregulation contributes to tumorigenesis.
Purpose of the Study:
- To review molecular targets associated with aberrant splicing across various malignancies.
- To discuss current and developing therapeutic strategies targeting aberrant RNA splicing.
- To outline future directions for drug development in this emerging field.
Main Methods:
- Literature review of studies on splicing factor mutations, splice site alterations, and their impact on cancer.
- Analysis of existing and emerging therapeutic agents targeting aberrant splicing mechanisms.
- Discussion of strategies for validating aberrant splicing patterns as therapeutic targets.
Main Results:
- Identified key molecular targets of aberrant splicing in diverse cancer types.
- Summarized the landscape of therapeutics, including antisense oligonucleotides and inhibitors of mutated splicing factors.
- Highlighted the need for improved delivery systems and specificity in therapeutic development.
Conclusions:
- Targeting aberrant RNA splicing represents an early but promising frontier in cancer treatment.
- Further research is required to characterize spliceosome aberrations, understand downstream pathways, and utilize in-vivo models.
- Advancements in drug delivery and specificity are crucial for the success of splicing-targeted cancer therapies.
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