Researchers identified a novel list of potential drugs to treat patients with intrahepatic cholangiocarcinoma (iCCA) and published their results in Cancers.

“The aim of our study was to identify possible novel therapeutic targets and drugs for [iCCA] by using transcriptomic profiles from the Gene Expression Omnibus databases and The Cancer Genome Atlas,” the authors of the study wrote.

A Connectivity Map database identified 9 potential drugs and other small molecules for iCCA treatment. Among these are 3 tyrosine kinase inhibitors, 2 antibiotics, including a fluoroquinolone and an aminopenicillin (moxifloxacin and amoxicillin), and 2 cannabinoid receptor agonists, 1 serine/threonine protein kinase inhibitor, and 1 estrogen receptor agonist.


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To complete this research, the authors obtained an RNA expression profile of patients previously diagnosed with iCCA and normal cells from the biliary epithelium to generate a weighted coexpression gene network that allowed to screen for hub genes and create a protein-protein interaction system.

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The 10 most screened hub genes included COL1A2, COL3A1, CTNNB1, GART, MRPS5, PKLR, SMAD3, SPP1, SRC, and VCAN served to assess their relationship with overall and disease-free survival in iCCA. To achieve the latter, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases aided in analyzing the function and enrichment pathways of all differentially expressed genes, as explained by Zhang and colleagues.

The results of this article are of great importance given that barely 15% of the patients newly diagnosed with iCCA are candidates for surgical resection.

In the remaining vast majority, pharmacological therapeutic schemes are inconclusive and usually ineffective. Being a disease with high mortality and an incidence that seems to be incrementing each year, targeted therapies are very much needed.

“Analyzing the hub genes, the drug candidate list of small molecules was created, and these could possibly be used as classes of novel pharmacologic agents for future studies to identify and develop innovative drugs for [iCCA] treatment,” the authors concluded.

Reference

Xiao Y, Zhang B, Cloyd J, et al. Novel drug candidate prediction for intrahepatic cholangiocarcinoma via hub gene network analysis and connectivity mapping. Cancers (Basel). Published online July 5, 2022. doi:10.3390/cancers14133284