Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma
3
Issued Date
2022-10-21
Resource Type
eISSN
25890042
Scopus ID
2-s2.0-85139665462
Journal Title
iScience
Volume
25
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
iScience Vol.25 No.10 (2022)
Suggested Citation
Jamnongsong S., Kueanjinda P., Buraphat P., Sakornsakolpat P., Vaeteewoottacharn K., Okada S., Jirawatnotai S., Sampattavanich S. Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma. iScience Vol.25 No.10 (2022). doi:10.1016/j.isci.2022.105182 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86463
Title
Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma
Other Contributor(s)
Abstract
Cholangiocarcinoma (CCA) is rare cancer with the highest incidence in Eastern and Southeast Asian countries. Advanced CCA patients rely on chemotherapeutic regimens that offer unsatisfied clinical outcomes. We developed a comprehensive drug response profiling to investigate potential new drugs using CCA cell lines from Thai and Japanese patients against 100 approved anti-cancer drugs. We identified two major CCA subgroups that displayed unique molecular pathways from our integrative pan-omic and ligand-induced pathway activation analyses. MEK and Src inhibitors specifically killed the CCA1 subgroup without causing cytotoxicity to the normal cholangiocyte. Next, we developed the CCA45 signature to classify CCA patients based on their transcriptomic data. Our CCA45 signature could accurately predict prognosis, especially for Asian CCA patients. Our study provides a comprehensive public resource for drug repurposing in CCA and introduces analytical strategies for prioritizing cancer therapeutic agents for other rare cancer.