Identification of Novel Key Targets and Candidate Drugs in Oral Squamous Cell Carcinoma

Author(s): Juan Liu, Xinjie Lian, Feng Liu, Xueling Yan, Chunyan Cheng, Lijia Cheng, Xiaolin Sun*, Zheng Shi*.

Journal Name: Current Bioinformatics

Volume 15 , Issue 4 , 2020

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Abstract:

Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant epithelial neoplasm. It is located within the top 10 ranking incidence of cancers with a poor prognosis and low survival rates. New breakthroughs of therapeutic strategies are therefore needed to improve the survival rate of OSCC harboring patients.

Objective: Since targeted therapy is considered as the most promising therapeutic strategies in cancer, it is of great significance to identify novel targets and drugs for the treatment of OSCC.

Methods: A series of bioinformatics approaches were launched to identify the hub proteins and their potential agents. Microarray analysis and several online functional activity network analysis were firstly utilized to recognize drug targets in OSCC. Subsequently, molecular docking was used to screen their potential drugs from the specs chemistry database. At the same time, the assessment of ligand-based virtual screening model was also evaluated.

Results: In this study, two microarray data (GSE31056, GSE23558) were firstly selected and analyzed to get consensus candidate genes including 681 candidate genes. Additionally, we selected 33 candidate genes based on whether they belong to the kinases and transcription factors and further clustered candidate hub targets based on functions and signaling pathways with significant enrichment analysis by using DAVID and STRING online databases. Then, core PPI network was then identified and we manually selected GRB2 and IGF1 as the key drug targets according to the network analysis and previous references. Lastly, virtual screening was performed to identify potential small molecules which could target these two targets, and such small molecules can serve as the promising candidate agents for future drug development.

Conclusion: In summary, our study might provide novel insights for understanding of the underlying molecular events of OSCC, and our discovered candidate targets and candidate agents could be used as the promising therapeutic strategies for the treatment of OSCC.

Keywords: Oral squamous cell carcinoma, novel target, GRB2, IGF1, systems biology, drug discovery.

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Article Details

VOLUME: 15
ISSUE: 4
Year: 2020
Page: [328 - 337]
Pages: 10
DOI: 10.2174/1574893614666191127101836