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有望用于宫颈癌药物再利用的候选靶基因:基于生物信息学的方法

Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach.

作者信息

Pratiwi Nurfi, Ulfah Aida J, Rachmadina Rachmadina, Irham Lalu M, Afief Arief R, Adikusuma Wirawan, Darmawi Darmawi, Kemal Rahmat A, Rangkuti Ina F, Savira Maya

机构信息

Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.

Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.

出版信息

Narra J. 2024 Dec;4(3):e938. doi: 10.52225/narra.v4i3.938. Epub 2024 Dec 12.

Abstract

Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, , , , , and were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Interestingly, talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer.

摘要

宫颈癌是全球女性中第四大常见癌症,研究表明基因变异在其发展过程中起着重要作用。多种种系和体细胞突变与宫颈癌相关。然而,源自这些突变的基因组数据尚未被广泛用于开发用于宫颈癌的重新利用药物。本研究的目的是通过生物信息学方法确定可重新用于宫颈癌治疗的新型潜在药物。采用了全面的基因组和生物信息学数据库整合策略来确定宫颈癌的潜在药物靶基因。利用全基因组关联研究(GWAS)和表型全基因组关联研究(PheWAS)数据库,共鉴定出232个与宫颈癌相关的基因。通过应用六个功能注释的生物学阈值进一步优化这些药理学靶基因。然后使用药物银行(DrugBank)数据库将药物靶基因与癌症治疗候选药物进行交叉参考。在鉴定出的基因中,[此处原文缺失具体基因名称]被突出显示为重新利用药物的有前景的靶点。值得注意的是,这五个靶基因与12种可能重新用于宫颈癌治疗的药物重叠。其中,强效聚(ADP-核糖)聚合酶(PARP)抑制剂他拉唑帕尼成为特别有前景的候选药物。有趣的是,他拉唑帕尼目前正在其他癌症中进行安全性和耐受性研究,但尚未在宫颈癌背景下进行研究。需要进一步的临床试验来验证这一发现,并探索其作为重新利用的宫颈癌药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e87/11731801/1f91d6c93d0b/NarraJ-4-e938-g001.jpg

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