Network-based drug repurposing for HPV-associated cervical cancer

Area of Science:

• Oncology
• Virology
• Computational Biology
• Pharmacology

Background:

• Cervical cancer (CC) is a significant global health concern, with human papillomavirus (HPV) types 16 and 18 implicated in approximately 50% of high-grade cases.
• HPV-positive patients face a substantially higher risk of CC, underscoring the need for effective and timely therapeutic interventions.
• Drug repurposing offers a cost-effective and time-efficient strategy for identifying novel treatments by leveraging existing pharmaceutical agents.

Purpose of the Study:

• To develop and apply an integrative drug repurposing framework utilizing a systems biology-enabled network medicine platform.
• To identify potential repurposable drugs and drug combinations for targeting HPV-induced cervical cancer pathways.
• To validate the efficacy of identified drug candidates through computational and transcriptomic analyses.

Main Methods:

• Construction of an HPV-induced CC protein interaction network (HPV2C) based on omics data from the GEO database.
• Modeling of a drug-target interaction (DTI) network using data from DrugBank and related resources.
• Network proximity analysis of HPV-host targets and DTIs within the human protein interactome to identify potential repurposable drugs.

Main Results:

• The framework identified 142 potential repurposable drugs targeting HPV-induced CC pathways.
• Of these, 51 drugs are already in clinical use for CC, and 33 possess antiviral activity.
• Gene set enrichment analysis and transcriptomic data validation confirmed the predictions, and 13 drug combinations were identified based on overlapping exposure.

Conclusions:

• The study presents an effective network-based methodology for the rapid identification of repurposable drugs and drug combinations against HPV-associated CC.
• This approach accelerates the drug discovery pipeline, offering a promising avenue for developing novel therapeutic strategies.
• The identified drug candidates and combinations warrant further investigation for clinical application in cervical cancer treatment.