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Updated: May 6, 2026

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Clinical perspective on chemo-resistance and the role of RNA processing
Nancy L Krett1, Shuo Ma, Steven T Rosen
1Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA, n-krett@northwestern.edu.
Abstract:
Pre-messenger RNA splicing is significantly changed in cancer cells leading to the expression of cancer-specific transcripts. These transcripts have the potential to be used as cancer biomarkers and also as targets for new therapeutic approaches. In addition, the cancer-specific transcripts have the potential to alter the drug response of the cancer cells creating a chemo-resistant state. This later property of alternative splicing presents a challenge to clinicians in the design of effective therapeutic regimens. When a patient's cancer relapses it is frequently refractory to standard chemotherapies resulting in a poor clinical outcome. Therefore, understanding the mechanisms of how alternative splicing can lead to chemo-resistance is critical to the effective delivery of treatment. Here, we will discuss the impact of alternative splicing variants on drug metabolism and activation; on drug interactions with cell signaling pathways; and on cell death pathways in cancer therapeutics. In addition to the initial characterization of splicing variants, the mechanisms leading to alterations in splicing are being studied in the setting of chemo-resistance and will be discussed here. The promise of therapeutic intervention to obviate the impact of these splicing variants will significantly enhance treatment options for cancer patients.
Insights
Altered RNA splicing in cancer cells creates unique transcripts that can lead to drug resistance. Understanding these splicing changes is key to developing effective cancer therapies and improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pre-messenger RNA (mRNA) splicing alterations are hallmarks of cancer cells, producing cancer-specific transcripts.
- These aberrant transcripts can serve as cancer biomarkers and therapeutic targets.
- Alternative splicing contributes to chemo-resistance, complicating treatment strategies and leading to poor patient outcomes.
Purpose of the Study:
- To discuss the impact of alternative splicing variants on cancer therapeutics.
- To explore the mechanisms by which alternative splicing leads to chemo-resistance.
- To highlight the potential of therapeutic interventions targeting splicing variants.
Main Methods:
- Review of current literature on alternative splicing in cancer.
- Analysis of the role of splicing variants in drug metabolism, signaling pathways, and cell death.
- Investigation into the mechanisms driving splicing alterations in chemo-resistant cancers.
Main Results:
- Alternative splicing variants influence drug metabolism, activation, and interactions with cellular pathways.
- Splicing alterations can modulate cell death pathways, contributing to therapeutic resistance.
- Mechanisms underlying splicing changes in chemo-resistance are under active investigation.
Conclusions:
- Understanding alternative splicing is critical for overcoming chemo-resistance in cancer.
- Targeting cancer-specific splicing variants offers a promising avenue for novel therapeutic strategies.
- Developing therapies to counteract the effects of splicing variants can significantly improve cancer treatment options.
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