有希望的候选药物靶基因在宫颈癌的重新利用:基于生物信息学的方法。

Narra J Pub Date : 2024-12-01 Epub Date: 2024-12-12 DOI:10.52225/narra.v4i3.938
Nurfi Pratiwi, Aida J Ulfah, Rachmadina Rachmadina, Lalu M Irham, Arief R Afief, Wirawan Adikusuma, Darmawi Darmawi, Rahmat A Kemal, Ina F Rangkuti, Maya Savira
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引用次数: 0

摘要

宫颈癌是全球女性中第四大常见癌症,研究表明,基因变异在其发展中起着重要作用。多种生殖系和体细胞突变与宫颈癌有关。然而,从这些突变中获得的基因组数据尚未广泛用于开发用于宫颈癌的重新用途药物。本研究的目的是通过生物信息学方法确定可能用于宫颈癌治疗的新型潜在药物。采用全面的基因组和生物信息学数据库整合策略,确定宫颈癌潜在的药物靶基因。利用GWAS和PheWAS数据库,共鉴定出232个与宫颈癌相关的基因。这些药理学靶基因通过应用六个功能注释的生物学阈值进一步细化。然后,药物靶基因与药物银行数据库中的癌症治疗候选基因进行交叉比对。在所鉴定的基因中,LTA、TNFRSF1A、PRKCZ、PDE4B和PARP被强调为再利用药物的有希望靶点。值得注意的是,这5个靶基因与12种可能用于宫颈癌治疗的药物重叠。其中,talazoparib,一种有效的PARP抑制剂,成为特别有希望的候选药物。有趣的是,目前正在研究talazoparib在其他癌症中的安全性和耐受性,但尚未在宫颈癌中进行研究。进一步的临床试验是必要的,以验证这一发现,并探索其潜力,作为一个重新用途的药物宫颈癌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach.

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, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP 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.

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