Making Way for Suppressing the FGF19/FGFR4 Axis in Cancer

References

• Presta M Chiodelli P Giacomini A Rusnati M Ronca R . Fibroblast growth factors (FGFs) in cancer: FGF traps as a new therapeutic approach. Pharmacol. Ther.179, 171 – 187 (2017).
   PubMed Web of Science ®Google Scholar
• Katoh M . Therapeutics targeting FGF signaling network in human diseases. Trends Pharmacol. Sci.37 (12), 1081 – 1096 (2016).
   PubMed Web of Science ®Google Scholar
• Belov AA Mohammadi M . Molecular mechanisms of fibroblast growth factor signaling in physiology and pathology. Cold Spring Harb. Perspect. Biol.5 (6), a015958 (2013).
   PubMed Web of Science ®Google Scholar
• Itoh N Ornitz DM . Evolution of the FGF and FGFR gene families. Trends Genet.20 (11), 563 – 569 (2004).
   PubMed Web of Science ®Google Scholar
• Jahn D Rau M Hermanns HM Geier A . Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease. Cytokine Growth Factor Rev.26 (6), 625 – 635 (2015).
   PubMed Web of Science ®Google Scholar
• Katoh M Katoh M . Evolutionary conservation of CCND1-ORAOV1-FGF19-FGF4 locus from zebrafish to human. Int. J. Mol. Med.12 (1), 45 – 50 (2003).
   PubMed Web of Science ®Google Scholar
• Inagaki T Choi M Moschetta A et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab.2 (4), 217 – 225 (2005).
   PubMed Web of Science ®Google Scholar
• Alvarez-Sola G Uriarte I Ujue-Latasa M et al. Fibroblast growth factor 15/19 in hepatocarcinogenesis. Dig. Dis.35 (3), 158 – 165 (2017).
   PubMed Web of Science ®Google Scholar
• Li Z Lin B Lin G et al. Circulating FGF19 closely correlates with bile acid synthesis and cholestasis in patients with primary biliary cirrhosis. PLoS ONE12 (6), e0178580 (2017).
   PubMed Web of Science ®Google Scholar
• Kir S Beddow SA Samuel VT et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science (80-)331 (6024), 1621 – 1624 (2011).
   PubMed Web of Science ®Google Scholar
• Kliewer SA Mangelsdorf DJ . Bile acids as hormones: the FXR-FGF15/19 pathway. Dig. Dis.33 (3), 327 – 331 (2015).
   PubMed Web of Science ®Google Scholar
• Bhatnagar S Damron HA Hillgartner FB . Fibroblast growth factor-19, a novel factor that inhibits hepatic fatty acid synthesis. J. Biol. Chem.284 (15), 10023 – 10033 (2009).
   PubMed Web of Science ®Google Scholar
• Kir S Kliewer SA Mangelsdorf DJ . Roles of FGF19 in liver metabolism roles of FGF19 in liver metabolism. Cold Spring Harb. Symp. Quant. Biol.76, 139 – 144 (2011).
   PubMedGoogle Scholar
• Potthoff MJ Boney-Montoya J Choi M et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. Cell Metab.13 (6), 729 – 738 (2011).
   PubMed Web of Science ®Google Scholar
• Schaap FG . Role of fibroblast growth factor 19 in the control of glucose homeostasis. Curr. Opin. Clin. Nutr. Metab. Care15 (4), 386 – 391 (2012).
   PubMed Web of Science ®Google Scholar
• Kurosu H Choi M Ogawa Y et al. Tissue-specific expression of βklotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J. Biol. Chem.282 (37), 26687 – 26695 (2007).
   PubMed Web of Science ®Google Scholar
• Owen BM Mangelsdorf DJ Kliewer SA . Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol. Metab.26 (1), 22 – 29 (2015).
   PubMed Web of Science ®Google Scholar
• Morton GJ Matsen ME Bracy DP et al. FGF19 action in the brain induces insulin-independent glucose lowering. J. Clin. Invest.123 (11), 4799 – 4808 (2013).
   PubMed Web of Science ®Google Scholar
• Sohn J-W . Network of hypothalamic neurons that control appetite. BMB Rep.48 (4), 229 – 233 (2015).
   PubMed Web of Science ®Google Scholar
• Marcelin G Jo Y-H Li X et al. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol. Metab.3 (1), 19 – 28 (2013).
   PubMed Web of Science ®Google Scholar
• Benoit B Meugnier E Castelli M et al. Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat. Med.23 (8), 990 – 996 (2017).
   PubMed Web of Science ®Google Scholar
• Glass DJ . What's so special about FGF19-unique effects reported on skeletal muscle mass and function. Cell Metab.26 (2), 287 – 288 (2017).
   PubMed Web of Science ®Google Scholar
• Repana D Ross P . Targeting FGF19/FGFR4 pathway: a novel therapeutic strategy for hepatocellular carcinoma. Diseases3 (4), 294 – 305 (2015).
   PubMedGoogle Scholar
• Fon Tacer K Bookout AL Ding X et al. Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol. Endocrinol.24 (10), 2050 – 2064 (2010).
   PubMedGoogle Scholar
• Torre LA Bray F Siegel RL Ferlay J Lortet-Tieulent J Jemal A . Global cancer statistics, 2012. CA Cancer J. Clin.65 (2), 87 – 108 (2015).
   PubMed Web of Science ®Google Scholar
• Prieto-Domínguez N Méndez-Blanco C Carbajo-Pescador S et al. Melatonin enhances sorafenib actions in human hepatocarcinoma cells by inhibiting mTORC1/p70S6K/HIF-1α and hypoxia-mediated mitophagy. Oncotarget8 (53), 91402 – 91414 (2017).
   PubMedGoogle Scholar
• Prieto-Domínguez N Ordóñez R Fernández A et al. Melatonin-induced increase in sensitivity of human hepatocellular carcinoma cells to sorafenib is associated with reactive oxygen species production and mitophagy. J. Pineal Res.61 (3), 396 – 407 (2016).
   PubMed Web of Science ®Google Scholar
• Torrecilla S Llovet JM . New molecular therapies for hepatocellular carcinoma. Clin. Res. Hepatol. Gastroenterol.39 (Suppl. 1), S80 – S85 (2015).
   PubMed Web of Science ®Google Scholar
• Gao Q Wang Z-C Duan M et al. Cell culture system for analysis of genetic heterogeneity within hepatocellular carcinomas and response to pharmacologic agents. Gastroenterology152 (1), 232 – 242 (2017).
   PubMed Web of Science ®Google Scholar
• Sawey ET Chanrion M Cai C et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by oncogenomic screening. Cancer Cell19 (3), 347 – 358 (2011).
   PubMed Web of Science ®Google Scholar
• Miura S Mitsuhashi N Shimizu H et al. Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma. BMC Cancer12, 56 (2012).
   PubMed Web of Science ®Google Scholar
• Hyeon J Ahn S Lee JJ Song DH Park C-K . Expression of fibroblast growth factor 19 is associated with recurrence and poor prognosis of hepatocellular carcinoma. Dig. Dis. Sci.58 (7), 1916 – 1922 (2013).
   PubMed Web of Science ®Google Scholar
• Uriarte I Latasa MU Carotti S et al. Ileal FGF15 contributes to fibrosis-associated hepatocellular carcinoma development. Int. J. Cancer136 (10), 2469 – 2475 (2015).
   PubMed Web of Science ®Google Scholar
• Zhou M Luo J Chen M et al. Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15. J. Hepatol.66 (6), 1182 – 1192 (2017).
   PubMed Web of Science ®Google Scholar
• Zhou M Yang H Learned RM Tian H Ling L . Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis. Nat. Commun.8, 15433 (2017).
   PubMed Web of Science ®Google Scholar
• Wan ZY Tian JS Tan HWS et al. Mechanistic target of rapamycin complex 1 is an essential mediator of metabolic and mitogenic effects of fibroblast growth factor 19 in hepatoma cells. Hepatology64 (4), 1289 – 1301 (2016).
   PubMed Web of Science ®Google Scholar
• Zhao H Lv F Liang G et al. FGF19 promotes transition in hepatocellular carcinoma cells by modulating the GSK3β/β-catenin signaling cascade via FGFR4 activation. Oncotarget7 (12), 13575 – 13586 (2015).
   Google Scholar
• Ho HK Pok S Streit S et al. Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention. J. Hepatol.50 (1), 118 – 127 (2009).
   PubMed Web of Science ®Google Scholar
• Chen Z Xie B Zhu Q et al. FGFR4 and TGF-β1 expression in hepatocellular carcinoma: correlation with clinicopathological features and prognosis. Int. J. Med. Sci.10 (13), 1868 – 1875 (2013).
   PubMed Web of Science ®Google Scholar
• Nagamatsu H Teishima J Goto K et al. FGF19 promotes progression of prostate cancer. Prostate75 (10), 1092 – 1101 (2015).
   PubMed Web of Science ®Google Scholar
• Desnoyers LR Pai R Ferrando RE et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene27 (1), 85 – 97 (2008).
   PubMed Web of Science ®Google Scholar
• Wang S Zhao D Tian R et al. FGF19 contributes to tumor progression in gastric cancer by promoting migration and invasion. Oncol. Res.23 (4), 197 – 203 (2016).
   PubMed Web of Science ®Google Scholar
• Chenau J Michelland S De Fraipont F et al. The cell line secretome, a suitable tool for investigating proteins released in vivo by tumors: application to the study of p53-modulated proteins secreted in lung cancer cells. J. Proteome Res.8 (10), 4579 – 4591 (2009).
   PubMed Web of Science ®Google Scholar
• Buhmeida A Dallol A Merdad A et al. High fibroblast growth factor 19 (FGF19) expression predicts worse prognosis in invasive ductal carcinoma of breast. Tumor Biol.35 (3), 2817 – 2824 (2014).
   PubMedGoogle Scholar
• Dallol A Buhmeida A Merdad A et al. Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast. Tumor Biol.36 (12), 9677 – 9683 (2015).
   PubMedGoogle Scholar
• Heilmann AM Subbiah V Wang K et al. Comprehensive genomic profiling of clinically advanced medullary thyroid carcinoma. Oncology90 (6), 339 – 346 (2016).
   PubMed Web of Science ®Google Scholar
• Zhang X Wang Z Tian L Xie J Zou G Jiang F . Increased expression of FGF19 contributes to tumor progression and cell motility of human thyroid cancer. Otolaryngol. Neck Surg.154 (1), 52 – 58 (2016).
   PubMed Web of Science ®Google Scholar
• St Bernard R Zheng L Liu W Winer D Asa SL Ezzat S . Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology146 (3), 1145 – 1153 (2005).
   PubMed Web of Science ®Google Scholar
• Xu Y-F Yang X-Q Lu X-F et al. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma. Biochem. Biophys. Res. Commun.446 (1), 54 – 60 (2014).
   PubMed Web of Science ®Google Scholar
• Spinola M Leani V Pignatiello C et al. Functional FGFR4 Gly388Arg polymorphism predicts prognosis in lung adenocarcinoma patients. J. Clin. Oncol.23 (29), 7307 – 7311 (2005).
   PubMed Web of Science ®Google Scholar
• Bange J Prechtl D Cheburkin Y et al. Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Res.62 (3), 840 – 847 (2002).
   PubMed Web of Science ®Google Scholar
• Wang J Stockton DW Ittmann M . The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression. Clin. Cancer Res.10 (18 Pt 1), 6169 – 6178 (2004).
   PubMed Web of Science ®Google Scholar
• Schreuder TCMA Marsman HA Lenicek M et al. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am. J. Physiol. Gastrointest. Liver Physiol.298 (3), G440 – G445 (2010).
   PubMed Web of Science ®Google Scholar
• Wojcik M Janus D Dolezal-Oltarzewska K et al. A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents. J. Pediatr. Endocrinol. Metab.25 (11–12), 1089 – 1093 (2012).
   PubMed Web of Science ®Google Scholar
• Wunsch E Milkiewicz M Wasik U et al. Expression of hepatic fibroblast growth factor 19 is enhanced in primary biliary cirrhosis and correlates with severity of the disease. Sci. Rep.5, 13462 (2015).
   PubMed Web of Science ®Google Scholar
• Lenicek M Duricova D Komarek V et al. Bile acid malabsorption in inflammatory bowel disease: assessment by serum markers. Inflamm. Bowel Dis.17 (6), 1322 – 1327 (2011).
   PubMed Web of Science ®Google Scholar
• Nolan JD Johnston IM Pattni SS Dew T Orchard TR Walters JRF . Diarrhea in Crohn's disease: investigating the role of the ileal hormone fibroblast growth factor 19. J. Crohn's Colitis9 (2), 125 – 131 (2015).
   Google Scholar
• Barutcuoglu B Basol G Cakir Y et al. Fibroblast growth factor-19 levels in Type 2 diabetic patients with metabolic syndrome. Ann. Clin. Lab. Sci.41 (4), 390 – 396 (2011).
   PubMed Web of Science ®Google Scholar
• Wang C Yang C Chang JY et al. Hepatocyte FRS2α is essential for the endocrine fibroblast growth factor to limit the amplitude of bile acid production induced by prandial activity. Curr. Mol. Med.14 (6), 703 – 711 (2014).
   PubMed Web of Science ®Google Scholar
• Jung D York JP Wang L et al. FXR-induced secretion of FGF15/19 inhibits CYP27 expression in cholangiocytes through p38 kinase pathway. Eur. J. Physiol.466 (5), 1011 – 1019 (2014).
   PubMed Web of Science ®Google Scholar
• Song K-H Li T Owsley E Strom S Chaing JYL . Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7α-hydroxylase gene expression. Hepatology49 (1), 297 – 305 (2009).
   PubMed Web of Science ®Google Scholar
• Shin D-J Osborne TF . FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. J. Biol. Chem.284 (17), 11110 – 11120 (2009).
   PubMed Web of Science ®Google Scholar
• Hu L Cong L . Fibroblast growth factor 19 is correlated with an unfavorable prognosis and promotes progression by activating fibroblast growth factor receptor 4 in advanced-stage serous ovarian cancer. Oncol. Rep.34 (5), 2683 – 2691 (2015).
   PubMed Web of Science ®Google Scholar
• Shi S Zhang Q Xia Y et al. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression. Am. J. Cancer Res.6 (2), 459 – 472 (2016).
   PubMed Web of Science ®Google Scholar
• Drafahl KA McAndrew CW Meyer AN Haas M Donoghue DJ . The receptor tyrosine kinase FGFR4 negatively regulates NF-κB signaling. PLoS ONE5 (12), e14412 (2010).
   PubMed Web of Science ®Google Scholar
• Pai R Dunlap D Qing J Mohtashemi I Hotzel K French DM . Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating β-catenin signaling. Cancer Res.68 (13), 5086 – 5095 (2008).
   PubMed Web of Science ®Google Scholar
• Zhao H Lv F Liang G et al. FGF19 promotes epithelial–mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β-catenin signaling cascade via FGFR4 activation. Oncotarget7 (12), 13575 – 13586 (2015).
   Google Scholar
• Teng Y Zhao H Gao L Zhang W Shull AY Shay C . FGF19 protects hepatocellular carcinoma cells against endoplasmic reticulum stress via activation of FGFR4-GSK3β-Nrf2 signaling. Cancer Res.77 (22), 6215 – 6225 (2017).
   PubMed Web of Science ®Google Scholar
• Zhou M Wang X Phung V et al. Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19. Cancer Res.74 (12), 3306 – 3317 (2014).
   PubMed Web of Science ®Google Scholar
• Katoh M . FGFR inhibitors: effects on cancer cells, tumor microenvironment and whole-body homeostasis (review). Int. J. Mol. Med.38 (1), 3 – 15 (2016).
   PubMed Web of Science ®Google Scholar
• Guagnano V Kauffmann A Wöhrle S et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov.2 (12), 1118 – 1133 (2017).
   Google Scholar
• Li SQ Cheuk AT Shern JF et al. Targeting wild-type and mutationally activated FGFR4 in rhabdomyosarcoma with the inhibitor ponatinib. PLoS ONE8 (10), e76551 (2013).
   PubMed Web of Science ®Google Scholar
• Lesca E Lammens A Huber R Augustin M . Structural analysis of the human fibroblast growth factor receptor 4 kinase. J. Mol. Biol.426 (22), 3744 – 3756 (2014).
   PubMed Web of Science ®Google Scholar
• Huang Z Tan L Wang H et al. DFG-out mode of inhibition by an irreversible type – 1 inhibitor capable of overcoming gate-keeper mutations in FGF receptors. ACS Chem. Biol.10 (1), 299 – 309 (2015).
   PubMed Web of Science ®Google Scholar
• Tan L Wang J Tanizaki J et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc. Natl Acad. Sci. USA111 (45), E4869 – E4877 (2014).
   PubMed Web of Science ®Google Scholar
• Wu D Guo M Philips MA et al. Crystal structure of the FGFR4/LY2874455 complex reveals insights into the pan-FGFR selectivity of LY2874455. PLoS ONE11 (9), e162491 (2016).
   PubMed Web of Science ®Google Scholar
• Michael M Bang Y Park YS et al. A Phase I study of LY2874455, an oral selective pan-FGFR inhibitor, in patients with advanced cancer. Target. Oncol.12 (4), 463 – 474 (2017).
   PubMed Web of Science ®Google Scholar
• Perera TPS Jovcheva E Mevellec L et al. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small-molecule FGFR family inhibitor. Mol. Cancer Ther.16 (6), 1010 – 1020 (2017).
   PubMed Web of Science ®Google Scholar
• Tabernero J Bahleda R Dienstmann R et al. Phase I dose-escalation study of JNJ-42756493, an oral pan–fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J. Clin. Oncol.33 (30), 3401 – 3408 (2017).
   Web of Science ®Google Scholar
• André F Cortés J . Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. Breast Cancer Res. Treat.150 (1), 1 – 8 (2015).
   PubMed Web of Science ®Google Scholar
• Peláez-García A Barderas R Torres S et al. FGFR4 role in epithelial–mesenchymal transition and its therapeutic value in colorectal cancer. PLoS ONE8 (5), e63695 (2013).
   PubMed Web of Science ®Google Scholar
• Wang Y Chen Z Dai M et al. Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping. Bioorg. Med. Chem. Lett.27 (11), 2420 – 2423 (2017).
   PubMed Web of Science ®Google Scholar
• Mo C Zhang Z Guise CP et al. 2-Aminopyrimidine derivatives as new selective fibroblast growth factor receptor 4 (FGFR4) inhibitors. ACS Med. Chem. Lett.8 (5), 543 – 548 (2017).
   PubMed Web of Science ®Google Scholar
• Hagel M Miduturu C Sheets M et al. First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway. Cancer Discov.5 (4), 424 – 437 (2015).
   PubMed Web of Science ®Google Scholar
• Packer LM Pollock PM . Paralog-specific kinase inhibition of FGFR4: adding to the arsenal of anti-FGFR agents. Cancer Discov.5 (4), 355 – 357 (2015).
   PubMed Web of Science ®Google Scholar
• Kim R Sharma S Meyer T et al. First-in-human study of BLU-554, a potent, highly-selective FGFR4 inhibitor designed for hepatocellular carcinoma (HCC) with FGFR4 pathway activation. Eur. J. Cancer69, S41 (2016).
   Web of Science ®Google Scholar
• French DM Lin BC Wang M et al. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models. PLoS ONE7 (5), e36713 (2012).
   PubMed Web of Science ®Google Scholar
• Tucker JA Klein T Breed J et al. Structural insights into FGFR kinase isoform selectivity: diverse binding modes of AZD4547 and ponatinib in complex with FGFR1 and FGFR4. Structure22 (12), 1764 – 1774 (2014).
   PubMed Web of Science ®Google Scholar
• Tiong KH Tan BS Choo HL et al. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival. Oncotarget7 (36), 57633 – 57650 (2016).
   PubMedGoogle Scholar
• Zhou M Learned RM Rossi SJ DePaoli AM Tian H Ling L . Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2-deficient mice. Hepatology63 (3), 914 – 929 (2016).
   PubMed Web of Science ®Google Scholar
• Ezzat S Zheng L Yu S Asa SL . A soluble dominant negative fibroblast growth factor receptor 4 isoform in human MCF-7 breast cancer cells. Biochem. Biophys. Res. Commun.287 (1), 60 – 65 (2001).
   PubMed Web of Science ®Google Scholar
• Gao L Wang X Tang Y Huang S Hu CA Teng Y . FGF19/FGFR4 signaling contributes to the resistance of hepatocellular carcinoma to sorafenib. J. Exp. Clin. Cancer Res.36 (1), 8 (2017).
   PubMedGoogle Scholar
• Gao L Shay C Lv F Wang X Teng Y . Implications of FGF19 on sorafenib-mediated nitric oxide production in hepatocellular carcinoma cells – a short report. Cell Oncol. (Dordr.)41 (1), 85 – 91 (2018).
   PubMed Web of Science ®Google Scholar
• Halatsch M-E Löw S Mursch K et al. Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. J. Neurosurg.111 (2), 211 – 218 (2009).
   PubMed Web of Science ®Google Scholar
• Wang W-B Yang Y Zhao Y-P Zhang T-P Liao Q Shu H . Recent studies of 5-fluorouracil resistance in pancreatic cancer. World J. Gastroenterol.20 (42), 15682 – 15690 (2014).
   PubMed Web of Science ®Google Scholar
• Turkington RC Longley DB Allen WL et al. Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer. Cell Death Dis.5 (2), e1046 (2014).
   PubMed Web of Science ®Google Scholar
• Ye Y-W Hu S Shi Y-Q et al. Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer. Oncol. Rep.30 (6), 2777 – 2784 (2013).
   PubMed Web of Science ®Google Scholar
• Shafei A El-Bakly W Sobhy A et al. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed. Pharmacother.95, 1209 – 1218 (2017).
   PubMed Web of Science ®Google Scholar
• Roidl A Berger H-J Kumar S Bange J Knyazev P Ullrich A . Resistance to chemotherapy is associated with fibroblast growth factor receptor 4 up-regulation. Clin. Cancer Res.15 (6), 2058 – 2066 (2009).
   PubMed Web of Science ®Google Scholar
• Guo Y Ding Y Zhang T An H . Sinapine reverses multi-drug resistance in MCF-7/dox cancer cells by downregulating FGFR4/FRS2α-ERK1/2 pathway-mediated NF-κB activation. Phytomedicine23 (3), 267 – 273 (2016).
   PubMed Web of Science ®Google Scholar
• Ahmed MA Selzer E Dörr W et al. Fibroblast growth factor receptor 4 induced resistance to radiation therapy in colorectal cancer. Oncotarget7 (43), 69976 – 69990 (2016).
   PubMedGoogle Scholar
• Santoro A Rimassa L Borbath I et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled Phase II study. Lancet Oncol.14 (1), 55 – 63 (2013).
   PubMed Web of Science ®Google Scholar
• Glen H . Pazopanib for the treatment of patients with advanced renal cell carcinoma. Future Oncol.12 (19), 2195 – 2204 (2016).
   PubMed Web of Science ®Google Scholar
• Pai R French D Ma N et al. Antibody-mediated inhibition of fibroblast growth factor 19 results in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys. Toxicol. Sci.126 (2), 446 – 456 (2012).
   PubMed Web of Science ®Google Scholar