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Author Spotlight: Exploring Advanced Therapeutic Targets in Osteosarcoma Through Spatial Transcriptomics
Published on: May 3, 2024
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Potential target identification for osteosarcoma treatment: Gene expression re-analysis and drug repurposing
Rawikant Kamolphiwong1, Kanyanatt Kanokwiroon1, Weerinrada Wongrin2
1Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Gene
|December 13, 2022
Summary
Drug repurposing offers new hope for osteosarcoma treatment by identifying novel drug targets and existing medications. This study highlights KLHL13 as a potential target and suggests niclosamide for repurposing to improve patient survival rates.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Osteosarcoma survival rates have stagnated for 30 years, necessitating novel therapeutic strategies.
- Drug repurposing accelerates the discovery of new treatments by identifying new uses for existing drugs, saving time and cost.
- Gene expression profiling and data mining are powerful tools for identifying potential therapeutic targets.
Purpose of the Study:
- To identify novel drug targets and repurposable drugs for osteosarcoma through data mining of gene expression profiles.
- To explore the potential of drug repurposing to improve osteosarcoma treatment outcomes.
- To validate identified targets and drugs using bioinformatics and pathway analysis.
Main Methods:
- Data mining of gene expression profiles, categorizing data into pathophysiology and metastasis groups.
- Differential gene expression analysis to identify primary candidate genes (PCGs) with significant fold change and adjusted p-value.
- Protein-protein interaction analysis, upstream transcription factor, and related-protein kinase identification to determine secondary candidate genes (SCGs).
- Matching PCGs and SCGs with drugs from the Drug Repurposing Hub.
Main Results:
- Identified 778 potential targets (360 PCGs, 418 SCGs), including the novel target KLHL13, which was upregulated in clinical samples.
- Matched 256 drugs (50 anti-cancer, 206 non-anti-cancer) with identified targets.
- Confirmed ongoing clinical trials for osteosarcoma using drugs targeting CDK4, BCL-2, JUN, SRC, and PIK3CA.
- Identified niclosamide and synthetic PPARγ ligands as promising candidates for drug repurposing.
Conclusions:
- Re-analysis of gene expression data can effectively identify new therapeutic targets and repurposable drugs for osteosarcoma.
- KLHL13 represents a novel candidate target for osteosarcoma therapy.
- Drug repurposing holds significant potential for advancing osteosarcoma treatment and improving patient survival.

