Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Computer Science and Information Technology, Institute for Advanced Studies in Basic Sciences, Zanjan, Iran.
Arch Biochem Biophys. 2021 Nov 15;712:109043. doi: 10.1016/j.abb.2021.109043. Epub 2021 Sep 29.
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) L1000CDS 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.
人表皮生长因子受体 2（HER2）阳性乳腺癌约占所有浸润性乳腺癌的 15-30%。尽管最近在治疗 HER2 亚型方面取得了进展，但耐药性和肿瘤复发仍然是主要问题。药物发现是一个漫长而困难的过程，因此本研究的目的是为现有治疗剂寻找潜在的新应用。从癌症基因组图谱（TCGA）数据库中检索了乳腺浸润性癌的基因表达数据。使用 LIMMA R 包对正常和肿瘤样本进行分析，以找到差异表达基因（DEGs）。这些基因被用作集成网络细胞特征库（LINCS）L1000CDS 软件的库的入口，并提出了 24 种重新利用的药物。根据获得的结果，其中一些药物，包括伏立诺他、莫西替坦、阿伐维啶、CGP-60474、BMS-387032、AT-7519 和姜黄素，与 FDA 批准的乳腺癌药物具有显著的功能相似性和结构相关性。基于由重新利用的药物及其靶基因组成的药物-靶标网络，上述药物的度数最高。此外，实验方法验证了姜黄素是治疗 HER2 阳性乳腺癌的有效治疗剂。因此，我们的工作表明，基于基因表达数据的一些重新利用的药物可以被认为是治疗 HER2 阳性乳腺癌的潜在药物。
