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• W4361236224 abstract "<div>Abstract<p>Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1–3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. <i>Cancer Res; 77(24); 6999–7013. ©2017 AACR</i>.</p></div>" @default.
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• W4361236224 date "2023-03-31" @default.
• W4361236224 modified "2023-09-30" @default.
• W4361236224 title "Data from H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma" @default.
• W4361236224 doi "https://doi.org/10.1158/0008-5472.c.6509454" @default.
• W4361236224 hasPublicationYear "2023" @default.
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