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Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach
Nurfi Pratiwi1,2, Aida J Ulfah1, Rachmadina Rachmadina1
1Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
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, 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.
Insights
This study identifies potential repurposed drugs for cervical cancer by analyzing genetic data. Talazoparib, a PARP inhibitor, shows promise for treating cervical cancer, warranting further clinical investigation.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Cervical cancer is a leading global cancer in women, influenced by genetic variants.
- Germline and somatic mutations are implicated, but genomic data is underutilized for drug discovery.
- Repurposing existing drugs offers a faster route to novel cervical cancer treatments.
Purpose of the Study:
- To identify novel drug candidates for cervical cancer treatment using a bioinformatics approach.
- To leverage integrated genomic and bioinformatics databases for drug target identification.
- To explore the potential of repurposed drugs for cervical cancer therapy.
Main Methods:
- Integrated genomic and bioinformatics databases (GWAS, PheWAS, DrugBank).
- Identified 232 cervical cancer-associated genes using GWAS and PheWAS.
- Filtered genes based on functional annotations and cross-referenced with DrugBank for drug candidates.
Main Results:
- Five key target genes (LTA, TNFRSF1A, PRKCZ, PDE4B, PARP) were identified.
- Twelve potential repurposed drugs were linked to these targets.
- Talazoparib, a PARP inhibitor, was highlighted as a promising candidate for cervical cancer.
Conclusions:
- Bioinformatics analysis successfully identified potential repurposed drugs for cervical cancer.
- Talazoparib shows significant promise, though clinical trials are needed for validation.
- This approach can accelerate the development of new cervical cancer treatments.
