Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma

Supawan Jamnongsong; Patipark Kueanjinda; Pongsakorn Buraphat; Phuwanat Sakornsakolpat; Kulthida Vaeteewoottacharn; Seiji Okada; Siwanon Jirawatnotai; Somponnat Sampattavanich

doi:10.1016/j.isci.2022.105182

Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma

iScience. 2022 Sep 23;25(10):105182. doi: 10.1016/j.isci.2022.105182. eCollection 2022 Oct 21.

Authors

Supawan Jamnongsong¹, Patipark Kueanjinda^{1

2}, Pongsakorn Buraphat¹, Phuwanat Sakornsakolpat¹, Kulthida Vaeteewoottacharn³, Seiji Okada⁴, Siwanon Jirawatnotai¹, Somponnat Sampattavanich¹

Affiliations

¹ Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
² Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
³ Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
⁴ Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan.

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.

Keywords: Cancer; Cancer systems biology; Omics.