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Potentiating BSEP-mediated bile acid efflux reverses first-line tyrosine kinase inhibitor resistance in hepatocellular carcinoma.
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Potentiating BSEP-mediated bile acid efflux reverses first-line tyrosine kinase inhibitor resistance in hepatocellular carcinoma.
Wu Z, Wang Y, Yu B, Yu R, Chen M, Chen Z, Shan J, Ding Z, Li J, Jin X, Chen Y, Wang L, Zhu H, Zhu W, Pan Q, Zhang T, Zhang Y, Lv L, Wang L, Zhao Y
Abstract
Tyrosine kinase inhibitor (TKI) resistance limits therapy for hepatocellular carcinoma (HCC). Integrating RNA-seq and public cohort data, we found consistent downregulation of the bile salt export pump (BSEP/ABCB11) in TKI-resistant HCC associated with poorer prognosis and reduced clinical response. Functional in vitro and xenograft studies, using BSEP overexpression/knockdown and TKI-resistant cell lines plus targeted metabolomics, showed BSEP expression deficiency leads to intracellular accumu...
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