Potentiating BSEP-mediated bile acid efflux reverses first-line tyrosine kinase inhibitor resistance in hepatocellular carcinoma - PubMed
8 hours ago
- #Drug Resistance
- #Bile Acid Metabolism
- #Hepatocellular Carcinoma
- Downregulation of BSEP in TKI-resistant HCC is linked to poor prognosis and reduced treatment response.
- Deficient BSEP causes accumulation of bile acids like GCA, activating EGFR signaling and driving TKI resistance; restoring BSEP reverses this.
- UDCA reverses resistance by binding cortactin, reducing its methylation, promoting degradation, and enabling YY1 to activate BSEP transcription.
- Clinical data support the inverse relationship between BSEP and CTTN and the role of UDCA in modulating this axis.