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High-throughput drug screening on cancer cell lines has been the starting point behind important drug discoveries and affords the opportunity to explore drug repurposing systematically. However, despite these advancements, only a minority of patients respond to these drugs, underscoring the unmet need to expand the treatment options for HNSCC. In more recent years, two anti-PD1 immunotherapy drugs (pembrolizumab and nivolumab) have been approved for the treatment of recurrent and metastatic HNSCC.
Since 2006, the EGFR-targeting cetuximab remained the only approved molecular-targeted drug for HNSCC. Head and neck squamous cell carcinoma (HNSCC) is a deadly disease affecting more than 700,000 people worldwide 1, unfortunately, effective treatment options are still lacking. Our approach could also reveal insights for drug repurposing in other cancers. 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. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. 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. The integrative analysis confirmed that the average expression of EGFR ligands ( AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. 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.
Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking.