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HNCDrugResDb: a platform for deciphering drug resistance in head and neck cancers
Akhina Palollathil1, Revathy Nandakumar1,2, Mukhtar Ahmed3
1Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India.
Abstract:
Drug resistance poses a significant obstacle to the success of anti-cancer therapy in head and neck cancers (HNCs). We aim to develop a platform for visualizing and analyzing molecular expression alterations associated with HNC drug resistance. Through data mining, we convened differentially expressed molecules and context-specific signaling events involved in drug resistance. The driver genes, interaction networks and transcriptional regulations were explored using bioinformatics approaches. A total of 2364 differentially expressed molecules were identified in 78 distinct drug-resistant cells against 14 anti-cancer drugs, comprising 1131 mRNAs, 746 proteins, 62 lncRNAs, 257 miRNAs, 1 circRNA, and 166 post-translational modifications. Among these, 255 molecules were considerably, the signature driver genes of HNC drug resistance. Further, we also developed a landscape of signaling pathways and their cross-talk with diverse signaling modules involved in drug resistance. Additionally, a publicly-accessible database named "HNCDrugResDb" was designed with browse, query, and pathway explorer options to fetch and enrich molecular alterations and signaling pathways altered in drug resistance. HNCDrugResDb is also enabled with a Drug Resistance Analysis tool as an initial platform to infer the likelihood of resistance based on the expression pattern of driver genes. HNCDrugResDb is anticipated to have substantial implications for future advancements in drug discovery and optimization of personalized medicine approaches.
Insights
Drug resistance in head and neck cancers (HNCs) is a major challenge. This study identifies key molecules and pathways driving HNC drug resistance, creating a database for analysis and personalized medicine.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Drug resistance significantly hinders anti-cancer therapy efficacy in head and neck cancers (HNCs).
- Understanding molecular mechanisms of drug resistance is crucial for developing effective treatments.
Purpose of the Study:
- To develop a platform for visualizing and analyzing molecular expression changes linked to HNC drug resistance.
- To identify driver genes, signaling pathways, and regulatory networks involved in HNC drug resistance.
Main Methods:
- Data mining of molecular expression profiles from drug-resistant HNC cells.
- Bioinformatics approaches to analyze driver genes, interaction networks, and transcriptional regulations.
- Development of a publicly accessible database (HNCDrugResDb) with analysis tools.
Main Results:
- Identified 2364 differentially expressed molecules (mRNAs, proteins, lncRNAs, miRNAs, circRNA, post-translational modifications) across 78 drug-resistant cell lines and 14 drugs.
- Discovered 255 signature driver genes critical for HNC drug resistance.
- Mapped signaling pathways and their crosstalk, and developed the HNCDrugResDb with a Drug Resistance Analysis tool.
Conclusions:
- The study provides a comprehensive resource for understanding HNC drug resistance mechanisms.
- HNCDrugResDb facilitates exploration of molecular alterations and pathway dynamics.
- This resource is expected to advance drug discovery and personalized medicine strategies for HNCs.
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