Molecularly Guided Drug Repurposing for Cholangiocarcinoma: An Integrative Bioinformatic Approach

      Cholangiocarcinoma (CCA) has a complex immune microenvironment architecture, thus possessing challenges in its characterization and treatment. This study aimed to repurpose FDA-approved drugs for cholangiocarcinoma by transcriptomic-driven bioinformatic approach. We derived an immune-oncogenic signature consisting of 26 mortality-associated genes. Patients with high-expression signature had poorer overall survival (log-rank p < 0.001). Gene enrichment analysis revealed cell-cycle checkpoint regulation and inflammatory-immune response signaling pathways were enriched in this high-risk group. The integrative drug-gene network identified eight FDA-approved drugs as promising candidates, including Dasatinib a multi-kinase inhibitor currently investigated for advanced CCA with isocitrate-dehydrogenase mutations. This study proposes the use of the immune-oncogenic gene signature to identify high-risk CCA patients to guide treatment. Future preclinical and clinical studies are required to elucidate the therapeutic efficacy of the molecularly guided drugs as the adjunct therapy, aiming to improve the survival outcome.

Reference

Venkatraman S, Balasubramanian B, Pongchaikul P, Tohtong R, Chutipongtanate S.
Molecularly Guided Drug Repurposing for Cholangiocarcinoma: An Integrative Bioinformatic Approach.
Genes (Basel). 2022 Jan 29;13(2):271.

DOI: 10.3390/genes13020271