New insight into the anti-liver fibrosis effect of multitargeted tyrosine kinase inhibitors: From molecular target to clinical trials

Frontiers in Pharmacology

Volumn 6, Issue JAN, 2016, Pages

  Qu, Kai ^a   Huang, Zichao ^a,b   Lin, Ting ^a   Liu, Sinan ^a   Chang, Hulin ^a,c   Yan, Zhaoyong ^d   Zhang, Hongxin ^d   Liu, Chang ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

^b Shaanxi Cancer Hospital   (China)

^c SHAANXI PROVINCIAL PEOPLE S HOSPITAL   (China)

^d FOURTH MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Clinical trials; Liver fibrosis; Molecular mechanisms; Preclinical study; Tyrosine kinase inhibitors

Indexed keywords

ABELSON KINASE; BRIVANIB; CYCLIN DEPENDENT KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; FIBROBLAST GROWTH FACTOR RECEPTOR; IMATINIB; KRUPPEL LIKE FACTOR 6; NILOTINIB; PLATELET DERIVED GROWTH FACTOR BB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SORAFENIB; SUNITINIB; VASCULOTROPIN RECEPTOR; VATALANIB;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; AUTOPHOSPHORYLATION; CHEMOTAXIS; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); COLLAGEN SYNTHESIS; DRUG TARGETING; FIBROGENESIS; GASTROINTESTINAL STROMAL TUMOR; HEPATITIS C; HUMAN; LIVER BLOOD FLOW; LIVER CELL; LIVER CELL CARCINOMA; LIVER CIRCULATION; LIVER CIRRHOSIS; LIVER FAILURE; LIVER FIBROSIS; LIVER TOXICITY; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS (TOPIC); NON SMALL CELL LUNG CANCER; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PORTAL HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SHORT SURVEY; SIGNAL TRANSDUCTION; STELLATE CELL;

EID: 84961994366     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2015.00300     Document Type: Short Survey

References (71)

1. Abdollahi, A., Li, M., Ping, G., Plathow, C., Domhan, S., Kiessling, F., et al. (2005). Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J. Exp. Med. 201, 925-935. doi: 10.1084/jem.20041393
2. Adam, R., and Hoti, E. (2009). Liver transplantation: the current situation. Semin. Liver Dis. 29, 3-18. doi: 10.1055/s-0029-1192052
3. Akhmetshina, A., Venalis, P., Dees, C., Busch, N., Zwerina, J., Schett, G., et al. (2009). Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis. Arthritis Rheum. 60, 219-224. doi: 10.1002/art.24186
4. Almendro, V., Garcia-Recio, S., and Gascon, P. (2010). Tyrosine kinase receptor transactivation associated to G protein-coupled receptors. Curr. Drug Targets 11, 1169-1180. doi: 10.2174/138945010792006807
5. Arora, A., and Scholar, E. M. (2005). Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther. 315, 971-979. doi: 10.1124/jpet.105.084145
6. Awada, A., Hendlisz, A., Gil, T., Bartholomeus, S., Mano, M., de Valeriola, D., et al. (2005). Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br. J. Cancer 92, 1855-1861. doi: 10.1038/sj.bjc.6602584
7. Beyer, C., and Distler, J. H. (2013). Tyrosine kinase signaling in fibrotic disorders: translation of basic research to human disease. Biochim. Biophys. Acta 1832, 897-904. doi: 10.1016/j.bbadis.2012.06.008
8. Chang, C. C., Chuang, C. L., Lee, F. Y., Wang, S. S., Lin, H. C., Huang, H. C., et al. (2013). Sorafenib treatment improves hepatopulmonary syndrome in rats with biliary cirrhosis. Clin. Sci. (Lond.) 124, 457-466. doi: 10.1042/CS20120052
9. Clark, J. W., Eder, J. P., Ryan, D., Lathia, C., and Lenz, H. J. (2005). Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin. Cancer Res. 11, 5472-5480. doi: 10.1158/1078-0432.CCR-04-2658
10. Coriat, R., Gouya, H., Mir, O., Ropert, S., Vignaux, O., Chaussade, S., et al. (2011). Reversible decrease of portal venous flow in cirrhotic patients: a positive side effect of sorafenib. PLoS ONE 6:e16978. doi: 10.1371/journal.pone.0016978
11. Cross, T. J., Bagot, C., Portmann, B., Wendon, J., and Gillett, D. (2006). Imatinib mesylate as a cause of acute liver failure. Am. J. Hematol. 81, 189-192. doi: 10.1002/ajh.20486
12. Daniels, C. E., Wilkes, M. C., Edens, M., Kottom, T. J., Murphy, S. J., Limper, A. H., et al. (2004). Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J. Clin. Invest. 114, 1308-1316. doi: 10.1172/JCI19603
13. Druker, B. J. (2003). Imatinib mesylate in the treatment of chronic myeloid leukaemia. Exp. Opin. Pharmacother. 4, 963-971. doi: 10.1517/14656566.4.6.963
14. El-Agamy, D. S., Shebl, A. M., and Said, S. A. (2011). Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice. Inflammopharmacology 19, 307-316. doi: 10.1007/s10787-011-0092-6
15. Faivre, S., Demetri, G., Sargent, W., and Raymond, E. (2007). Molecular basis for sunitinib efficacy and future clinical development. Nat. Rev. Drug Discov. 6, 734-745. doi: 10.1038/nrd2380
16. Friedman, S. L. (2008). Mechanisms of hepatic fibrogenesis. Gastroenterology 134, 1655-1669. doi: 10.1053/j.gastro.2008.03.003
17. Fuchs, B. C., Hoshida, Y., Fujii, T., Wei, L., Yamada, S., Lauwers, G. Y., et al. (2014). Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma. Hepatology 59, 1577-1590. doi: 10.1002/hep.26898
18. Gonzalo, T., Beljaars, L., van de Bovenkamp, M., Temming, K., van Loenen, A. M., Reker-Smit, C., et al. (2007). Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells. J. Pharmacol. Exp. Ther. 321, 856-865. doi: 10.1124/jpet.106.114496
19. Grimminger, F., Schermuly, R. T., and Ghofrani, H. A. (2010). Targeting non-malignant disorders with tyrosine kinase inhibitors. Nat. Rev. Drug Discov. 9, 956-970. doi: 10.1038/nrd3297
20. Heldin, C. H. (2014). Targeting the PDGF signaling pathway in the treatment of non-malignant diseases. J. Neuroimmune Pharmacol. 9, 69-79. doi: 10.1007/s11481-013-9484-2
21. Hennenberg, M., Trebicka, J., Stark, C., Kohistani, A. Z., Heller, J., and Sauerbruch, T. (2009). Sorafenib targets dysregulated Rho kinase expression and portal hypertension in rats with secondary biliary cirrhosis. Br. J. Pharmacol. 157, 258-270. doi: 10.1111/j.1476-5381.2009.00158.x
22. Hernandez-Gea, V., and Friedman, S. L. (2011). Pathogenesis of liver fibrosis. Annu. Rev. Pathol. 6, 425-456. doi: 10.1146/annurev-pathol-011110-130246
23. Hong, F., Chou, H., Fiel, M. I., and Friedman, S. L. (2013). Antifibrotic activity of sorafenib in experimental hepatic fibrosis: refinement of inhibitory targets, dosing, and window of efficacy in vivo. Dig. Dis. Sci. 58, 257-264. doi: 10.1007/s10620-012-2325-y
24. Hsu, S. J., Hsin, I. F., Lin, Y. L., Chen, Y. C., Huang, H. C., Lee, F. Y., et al. (2012). The influence of sorafenib on hepatic encephalopathy and the mechanistic survey in cirrhotic rats. Eur. J. Clin. Invest. 42, 1309-1316. doi: 10.1111/eci.12006
25. Iacovelli, R., Palazzo, A., Procopio, G., Santoni, M., Trenta, P., De Benedetto, A., et al. (2014). Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy. Br. J. Clin. Pharmacol. 77, 929-938. doi: 10.1111/bcp.12231
26. Kuo, W. L., Yu, M. C., Lee, J. F., Tsai, C. N., Chen, T. C., and Chen, M. F. (2012). Imatinib mesylate improves liver regeneration and attenuates liver fibrogenesis in CCL4-treated mice. J. Gastrointest. Surg. 16, 361-369. doi: 10.1007/s11605-011-1764-7
27. Lathia, C., Lettieri, J., Cihon, F., Gallentine, M., Radtke, M., and Sundaresan, P. (2006). Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother. Pharmacol. 57, 685-692. doi: 10.1007/s00280-005-0068-6
28. Lee, J. S., and Kim, J. H. (2007). [The role of activated hepatic stellate cells in liver fibrosis, portal hypertension and cancer angiogenesis]. Korean J. Hepatol. 13, 309-319. doi: 10.3350/kjhep.2007.13.3.309
29. Lin, H. C., Huang, Y. T., Yang, Y. Y., Lee, P. C., Hwang, L. H., Lee, W. P., et al. (2014). Beneficial effects of dual vascular endothelial growth factor receptor/fibroblast growth factor receptor inhibitor brivanib alaninate in cirrhotic portal hypertensive rats. J. Gastroenterol. Hepatol. 29, 1073-1082. doi: 10.1111/jgh.12480
30. Liu, C., Yang, Z., Wang, L., Lu, Y., Tang, B., Miao, H., et al. (2015). Combination of sorafenib and gadolinium chloride (GdCl3) attenuates dimethylnitrosamine(DMN)-induced liver fibrosis in rats. BMC Gastroenterol. 15:159. doi: 10.1186/s12876-015-0380-5
31. Liu, Y., Lui, E. L., Friedman, S. L., Li, L., Ye, T., Chen, Y., et al. (2009a). PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo by inhibiting VEGF signaling. Lab. Invest. 89, 209-221. doi: 10.1038/labinvest.2008.127
32. Liu, Y., Wen, X. M., Lui, E. L., Friedman, S. L., Cui, W., Ho, N. P., et al. (2009b). Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258. Lab. Invest. 89, 1152-1160. doi: 10.1038/labinvest.2009.77
33. Liu, Y., Wang, Z., Kwong, S. Q., Lui, E. L., Friedman, S. L., Li, F. R., et al. (2011). Inhibition of PDGF, TGF-beta, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib. J. Hepatol. 55, 612-625. doi: 10.1016/j.jhep.2010.11.035
34. Llanos, L., Bellot, P., Zapater, P., Perez-Mateo, M., and Such, J. (2009). Acute hepatitis in a patient with cirrhosis and hepatocellular carcinoma treated with sorafenib. Am. J. Gastroenterol. 104, 257-258. doi: 10.1038/ajg.2008.41
35. Majumder, S., Piguet, A. C., Dufour, J. F., and Chatterjee, S. (2013). Study of the cellular mechanism of Sunitinib mediated inactivation of activated hepatic stellate cells and its implications in angiogenesis. Eur. J. Pharmacol. 705, 86-95. doi: 10.1016/j.ejphar.2013.02.026
36. Medina, J., Arroyo, A. G., Sanchez-Madrid, F., and Moreno-Otero, R. (2004). Angiogenesis in chronic inflammatory liver disease. Hepatology 39, 1185-1195. doi: 10.1002/hep.20193
37. Mejias, M., Garcia-Pras, E., Tiani, C., Miquel, R., Bosch, J., and Fernandez, M. (2009). Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats. Hepatology 49, 1245-1256. doi: 10.1002/hep.22758
38. Moore, M., Hirte, H. W., Siu, L., Oza, A., Hotte, S. J., Petrenciuc, O., et al. (2005). Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann. Oncol. 16, 1688-1694. doi: 10.1093/annonc/mdi310
39. Nakamura, I., Zakharia, K., Banini, B. A., Mikhail, D. S., Kim, T. H., Yang, J. D., et al. (2014). Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling. PLoS ONE 9:e92273. doi: 10.1371/journal.pone.0092273
40. Neef, M., Ledermann, M., Saegesser, H., Schneider, V., Widmer, N., Decosterd, L. A., et al. (2006). Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term. J. Hepatol. 44, 167-175. doi: 10.1016/j.jhep.2005.06.015
41. Peer, C. J., Sissung, T. M., Kim, A., Jain, L., Woo, S., Gardner, E. R., et al. (2012). Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia. Clin. Cancer Res. 18, 2099-2107. doi: 10.1158/1078-0432.CCR-11-2484
42. Pinter, M., Sieghart, W., Reiberger, T., Rohr-Udilova, N., Ferlitsch, A., and Peck-Radosavljevic, M. (2012). The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma-a pilot study. Aliment. Pharmacol. Ther. 35, 83-91. doi: 10.1111/j.1365-2036.2011.04896.x
43. Plastaras, J. P., Kim, S. H., Liu, Y. Y., Dicker, D. T., Dorsey, J. F., McDonough, J., et al. (2007). Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. 67, 9443-9454. doi: 10.1158/0008-5472.CAN-07-1473
44. Rosmorduc, O. (2010). Antiangiogenic therapies in portal hypertension: a breakthrough in hepatology. Gastroenterol. Clin. Biol. 34, 446-449. doi: 10.1016/j.gcb.2010.05.007
45. Rossler, J., Geoerger, B., Taylor, M., and Vassal, G. (2008). Small molecule tyrosine kinase inhibitors: potential role in pediatric malignant solid tumors. Curr. Cancer Drug. Targets 8, 76-85. doi: 10.2174/156800908783497113
46. Schramm, C., Schuch, G., and Lohse, A. W. (2008). Sorafenib-induced liver failure. Am. J. Gastroenterol. 103, 2162-2163. doi: 10.1111/j.1572-0241.2008.01982_19.x
47. Shah, R. R., Morganroth, J., and Shah, D. R. (2013). Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 36, 491-503. doi: 10.1007/s40264-013-0048-4
48. Shaker, M. E., Ghani, A., Shiha, G. E., Ibrahim, T. M., and Mehal, W. Z. (2013). Nilotinib induces apoptosis and autophagic cell death of activated hepatic stellate cells via inhibition of histone deacetylases. Biochim. Biophys. Acta 1833, 1992-2003. doi: 10.1016/j.bbamcr.2013.02.033
49. Shaker, M. E., Salem, H. A., Shiha, G. E., and Ibrahim, T. M. (2011a). Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression. Fundam. Clin. Pharmacol. 25, 248-257. doi: 10.1111/j.1472-8206.2010.00824.x
50. Shaker, M. E., Shiha, G. E., and Ibrahim, T. M. (2011b). Comparison of early treatment with low doses of nilotinib, imatinib and a clinically relevant dose of silymarin in thioacetamide-induced liver fibrosis. Eur. J. Pharmacol. 670, 593-600. doi: 10.1016/j.ejphar.2011.08.041
51. Shaker, M. E., Zalata, K. R., Mehal, W. Z., Shiha, G. E., and Ibrahim, T. M. (2011c). Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis. Toxicol. Appl. Pharmacol. 252, 165-175. doi: 10.1016/j.taap.2011.02.004
52. Shiha, G. E., Abu-Elsaad, N. M., Zalata, K. R., and Ibrahim, T. M. (2014). Tracking anti-fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: an insight. Clin. Exp. Pharmacol. Physiol. 41, 788-797. doi: 10.1111/1440-1681.12286
53. Stefano, J. T., Pereira, I. V., Torres, M. M., Bida, P. M., Coelho, A. M., Xerfan, M. P., et al. (2015). Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model. Braz. J. Med. Biol. Res. 48, 408-414. doi: 10.1590/1414-431X20143962
54. Strumberg, D., Clark, J. W., Awada, A., Moore, M. J., Richly, H., Hendlisz, A., et al. (2007). Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 12, 426-437. doi: 10.1634/theoncologist.12-4-426
55. Thabut, D., Routray, C., Lomberk, G., Shergill, U., Glaser, K., Huebert, R., et al. (2011). Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis. Hepatology 54, 573-585. doi: 10.1002/hep.24427
56. Thabut, D., and Shah, V. (2010). Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension? J. Hepatol. 53, 976-980. doi: 10.1016/j.jhep.2010.07.004
57. Theysohn, J. M., Schlaak, J. F., Muller, S., Ertle, J., Schlosser, T. W., Bockisch, A., et al. (2012). Selective internal radiation therapy of hepatocellular carcinoma: potential hepatopulmonary shunt reduction after sorafenib administration. J. Vasc. Interv. Radiol. 23, 949-952. doi: 10.1016/j.jvir.2012.04.007
58. Tomizawa, M., Shinozaki, F., Sugiyama, T., Yamamoto, S., Sueishi, M., and Yoshida, T. (2010). Sorafenib suppresses the cell cycle and induces the apoptosis of hepatocellular carcinoma cell lines in serum-free media. Exp. Ther. Med. 1, 863-866. doi: 10.3892/etm.2010.131
59. Tonyali, O., Coskun, U., Yildiz, R., Karakan, T., Demirci, U., Akyurek, N., et al. (2010). Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors. Med. Oncol. 27, 768-773. doi: 10.1007/s12032-009-9284-y
60. Tugues, S., Fernandez-Varo, G., Munoz-Luque, J., Ros, J., Arroyo, V., Rodes, J., et al. (2007). Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. Hepatology 46, 1919-1926. doi: 10.1002/hep.21921
61. Wang, S., Wilkes, M. C., Leof, E. B., and Hirschberg, R. (2005). Imatinib mesylate blocks a non-Smad TGF-beta pathway and reduces renal fibrogenesis in vivo. FASEB J. 19, 1-11. doi: 10.1096/fj.04-2370com
62. Wang, Y., Gao, J., Zhang, D., Zhang, J., Ma, J., and Jiang, H. (2010). New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis. J. Hepatol. 53, 132-144. doi: 10.1016/j.jhep.2010.02.027
63. Westra, I. M., Oosterhuis, D., Groothuis, G. M., and Olinga, P. (2014a). The effect of antifibrotic drugs in rat precision-cut fibrotic liver slices. PLoS ONE 9:e95462. doi: 10.1371/journal.pone.0095462
64. Westra, I. M., Oosterhuis, D., Groothuis, G. M., and Olinga, P. (2014b). Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs. Toxicol. Appl. Pharmacol. 274, 328-338. doi: 10.1016/j.taap.2013.11.017
65. Xu, A. M., and Huang, P. H. (2010). Receptor tyrosine kinase coactivation networks in cancer. Cancer Res. 70, 3857-3860. doi: 10.1158/0008-5472.CAN-10-0163
66. Yan, Z., Qu, K., Zhang, J., Huang, Q., Qu, P., Xu, X., et al. (2015). CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells. Clin. Sci (Lond.) 129, 699-710. doi: 10.1042/CS20140823
67. Yang, Y. Y., Liu, R. S., Lee, P. C., Yeh, Y. C., Huang, Y. T., Lee, W. P., et al. (2014). Anti-VEGFR agents ameliorate hepatic venous dysregulation/microcirculatory dysfunction, splanchnic venous pooling and ascites of NASH-cirrhotic rat. Liver Int. 34, 521-534. doi: 10.1111/liv.12299
68. Yoshiji, H., Kuriyama, S., Noguchi, R., Ikenaka, Y., Yoshii, J., Yanase, K., et al. (2006). Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-beta with a combination of imatinib mesylate and ACE inhibitor in rats. Int. J. Mol. Med. 17, 899-904.
69. Yoshiji, H., Kuriyama, S., Yoshii, J., Ikenaka, Y., Noguchi, R., Hicklin, D. J., et al. (2003). Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis. Gut 52, 1347-1354. doi: 10.1136/gut.52.9.1347
70. Yoshiji, H., Noguchi, R., Kuriyama, S., Ikenaka, Y., Yoshii, J., Yanase, K., et al. (2005). Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G907-G913. doi: 10.1152/ajpgi.00420.2004
71. Zander, T., and Hallek, M. (2011). Tyrosin kinase inhibitors in oncology. Internist 52, 595-600. doi: 10.1007/s00108-011-2818-3