Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis

Chai, Annie Wai Yeeng and Tan, Aik Choon and Cheong, Sok Ching (2021) Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis. Scientific Reports, 11 (1). p. 23933. ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-021-03418-1.

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Official URL: https://doi.org/10.1038/s41598-021-03418-1


Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers. © 2021, The Author(s).

Item Type: Article
Uncontrolled Keywords: Cancer genetics; Head and neck cancer; Oral cancer; Tumour biomarkers
Subjects: R Medicine
R Medicine > RK Dentistry
Divisions: Faculty of Dentistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 29 Dec 2021 03:44
Last Modified: 29 Dec 2021 03:44
URI: http://eprints.um.edu.my/id/eprint/26083

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