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Recent data suggest that the <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>19\u2010<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 axis may be a key driver in certain forms of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>, making the pathway an interesting, emerging molecular target for potential therapeutic intervention. A complication is that, outside of malignant disease, <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 plays an important physiological role in the regulation of hepatic bile acid (<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>) synthesis. <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>19 signalling via <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 suppresses <jats:italic>de novo <\/jats:italic><jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> production in the liver, tightly maintaining hepatic and systemic levels of these detergent\u2010like molecules at a physiological threshold and preventing pathological complications of raised <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> levels, such as cholestatic liver injury and bile acid diarrhoea. In some cases of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>, the malignant disease causes bile duct obstruction, preventing <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> secretion from the liver and resulting in cholestasis. Here, the role of <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 signalling in both <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> homoeostasis is discussed. The potential effects of therapeutic <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>19\u2010<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 inhibition on human hepatobiliary\/gastrointestinal physiology are considered along with the potential safety implications of <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>19\u2010<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>4 blockade in patients with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/liv.12462","type":"journal-article","created":{"date-parts":[[2014,1,2]],"date-time":"2014-01-02T18:10:17Z","timestamp":1388686217000},"source":"Crossref","is-referenced-by-count":42,"title":["Targeted inhibition of the <scp>FGF<\/scp>19\u2010<scp>FGFR<\/scp>4 pathway in hepatocellular carcinoma; translational safety considerations"],"prefix":"10.1111","volume":"34","author":[{"given":"Howard R.","family":"Mellor","sequence":"first","affiliation":[{"name":"Drug Safety &amp; Metabolism Innovative Medicines AstraZeneca R&amp;D Macclesfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2780"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90110-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.17.3221"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6332"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101603"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05526.x"},{"key":"e_1_2_8_8_1","first-page":"5164","article-title":"FGF19\u2010induced hepatocyte proliferation is mediated through FGFR4 activation","volume":"285","author":"Wu X","year":"2010","journal-title":"J Biol Chem"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016521"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704244200"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-56"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61177-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210623"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036713"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.20.15482"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.09.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21287"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.04.024"},{"key":"e_1_2_8_19_1","first-page":"267","article-title":"Icteric type hepatoma","volume":"4","author":"Lin TY","year":"1975","journal-title":"Med Chir Dig"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1665-2681(19)31582-0","article-title":"Advanced hepatocellular carcinoma. 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