Related Experiment Video
Updated: Oct 18, 2025
Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Drug repositioning based on gene expression data for human HER2-positive breast cancer
Farkhondeh Khanjani1, Leila Jafari2, Somayeh Azadiyan3
1Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents approximately 15-30% of all invasive breast cancers. Despite the recent advances in therapeutic practices of HER2 subtype, drug resistance and tumor recurrence still have remained as major problems. Drug discovery is a long and difficult process, so the aim of this study is to find potential new application for existing therapeutic agents. Gene expression data for breast invasive carcinoma were retrieved from The Cancer Genome Atlas (TCGA) database. The normal and tumor samples were analyzed using Linear Models for Microarray Data (LIMMA) R package in order to find the differentially expressed genes (DEGs). These genes were used as entry for the library of integrated network-based cellular signatures (LINCS) L1000CDS2 software and suggested 24 repurposed drugs. According to the obtained results, some of these drugs including vorinostat, mocetinostat, alvocidib, CGP-60474, BMS-387032, AT-7519, and curcumin have significant functional similarity and structural correlation with FDA-approved breast cancer drugs. Based on the drug-target network, which consisted of the repurposed drugs and their target genes, the aforementioned drugs had the highest degrees. Moreover, the experimental approach verified curcumin as an effective therapeutic agent for HER2 positive breast cancer. Hence, our work suggested that some repurposed drugs based on gene expression data can be noticed as potential drugs for the treatment of HER2-positive breast cancer.
Insights
This study repurposed existing drugs for HER2-positive breast cancer treatment by analyzing gene expression data. Curcumin showed effectiveness, suggesting potential new therapeutic applications for this challenging cancer subtype.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- HER2-positive breast cancer affects 15-30% of patients.
- Drug resistance and tumor recurrence remain significant challenges in HER2+ breast cancer therapy.
- Developing new drugs is a lengthy and complex process.
Purpose of the Study:
- To identify potential new applications for existing therapeutic agents in HER2-positive breast cancer.
- To leverage gene expression data for drug repurposing.
- To discover novel treatment strategies for drug-resistant HER2+ breast cancer.
Main Methods:
- Gene expression data for breast invasive carcinoma were obtained from The Cancer Genome Atlas (TCGA).
- Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data (LIMMA) R package.
- The LINCS L1000CDS2 software was utilized to identify 24 repurposed drugs based on DEGs.
Main Results:
- Several repurposed drugs, including vorinostat, mocetinostat, alvocidib, and curcumin, showed functional and structural similarities to approved breast cancer drugs.
- Network analysis highlighted specific repurposed drugs with high network degrees.
- Experimental validation confirmed curcumin's efficacy as a therapeutic agent for HER2-positive breast cancer.
Conclusions:
- Repurposed drugs identified through gene expression analysis show promise for treating HER2-positive breast cancer.
- Curcumin is a potential therapeutic candidate for HER2-positive breast cancer.
- This approach offers a faster route to discovering new treatments for difficult-to-treat breast cancer subtypes.
