CDCA

Overview

Chenodeoxycholic acid (CDCA) is a primary bile acid and endogenous agonist of the farnesoid X receptor (NR1H4 / FXR). In cholangiocarcinoma (CHOL), CDCA has a dual role: as a diagnostic biomarker (elevated serum CDCA+TCDCA panel reportedly outperforms CA19-9 for CCA vs benign biliary disease/HCC, AUC = 0.95) and as a potential therapeutic agent via FXR activation. IDH1/IDH2 mutations in iCCA epigenetically suppress bile acid synthesis genes including CYP7A1, indirectly impairing CDCA homeostasis.

Evidence in the corpus

• A serum CDCA+TCDCA diagnostic panel reportedly outperformed CA19-9 (AUC = 0.95) for distinguishing CCA from benign biliary disease and HCC (Zhang X, reviewed) PMID:25608663
• IDH1/IDH2 mutations in iCCA drive 2-hydroxyglutarate accumulation, epigenetically suppressing bile acid synthesis genes (e.g. CYP7A1) via DNA hypermethylation, disrupting endogenous CDCA homeostasis PMID:25608663
• Single-cell RNA-seq consensus clustering classified CCA into BA-active (elevated CDCA-related signaling, shorter OS, immunotherapy resistance) and BA-inactive subtypes PMID:25608663

Resistance mechanisms

Cancer types (linked)

• CHOL — cholangiocarcinoma (iCCA, pCCA, dCCA)

Sources

• PMID:25608663

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