Related Experiment Video
Updated: May 17, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Splice isoforms as therapeutic targets for colorectal cancer
Koh Miura1, Wataru Fujibuchi, Michiaki Unno
1Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. k-miura@surg1.med.tohoku.ac.jp
Abstract:
Alternative pre-mRNA splicing allows exons of pre-mRNA to be spliced in different arrangements to produce functionally distinct mRNAs. More than 95% of human genes encode splice isoforms, some of which exert antagonistic functions. Recent studies revealed that alterations of the splicing machinery can cause the development of neoplasms, and understanding the splicing machinery is crucial for developing novel therapeutic strategies for malignancies. Colorectal cancer patients need novel strategies not only to enhance the efficacy of the currently available agents but also to utilize newly identified therapeutic targets. This review summarizes the current knowledge about the splice isoforms of VEGFA, UGT1A, PXR, cyclin D1, BIRC5 (survivin), DPD, K-RAS, SOX9, SLC39A14 and other genes, which may be possible therapeutic targets for colorectal cancer. Among them, the VEGFA splice isoforms are classified into VEGFAxxx and VEGFAxxxb, which have proangiogenic and antiangiogenic properties, respectively; UGT1A is alternatively spliced into UGT1A1 and other isoforms, which are regulated by pregnane X receptor isoforms and undergo further splicing modifications. Recently, the splicing machinery has been extensively investigated and novel discoveries in this research field are being reported at a rapid pace. The information contained in this review also provides suggestions for how therapeutic strategies targeting alternative splicing can be further developed.
Insights
Alternative splicing in cancer generates distinct mRNA variants. Targeting these splice isoforms offers new therapeutic strategies for colorectal cancer, improving treatment efficacy and identifying novel targets.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Alternative pre-mRNA splicing produces functionally distinct messenger RNAs (mRNAs) from over 95% of human genes.
- Aberrations in splicing machinery are linked to neoplasm development, highlighting its importance in cancer therapy.
- Colorectal cancer (CRC) requires novel therapeutic strategies beyond current agents, necessitating the identification of new targets.
Purpose of the Study:
- To review current knowledge on splice isoforms of key genes in colorectal cancer.
- To identify potential therapeutic targets for colorectal cancer based on alternative splicing.
- To provide insights into developing novel therapeutic strategies targeting alternative splicing.
Main Methods:
- Literature review of studies on alternative splicing in colorectal cancer.
- Analysis of splice isoforms of genes including VEGFA, UGT1A, PXR, cyclin D1, BIRC5 (survivin), DPD, K-RAS, SOX9, and SLC39A14.
- Classification and functional characterization of identified splice isoforms.
Main Results:
- Identified splice isoforms of VEGFA (VEGFAxxx, VEGFAxxxb) with opposing angiogenic functions.
- Described alternative splicing of UGT1A isoforms regulated by pregnane X receptor (PXR) isoforms.
- Highlighted several genes whose splice isoforms represent potential therapeutic targets for colorectal cancer.
Conclusions:
- Alternative splicing plays a critical role in colorectal cancer pathogenesis.
- Targeting specific splice isoforms, such as VEGFA variants, offers promising therapeutic avenues.
- Further research into splicing machinery alterations can lead to the development of innovative colorectal cancer treatments.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Pharmacogenomics: Identification of New Drug Targets
RNA Splicing
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

